Now, just as a child’s milk teeth must one day be replaced by a larger, more permanent set of adult teeth, so the time has come for BMC Oral Health to move to a new editorial model to ensure it can continue to serve the needs of its community. From this week the journal will be divided up into ...

Read more]]> For over a decade, BMC Oral Health has been pioneering the open access model in dental research. From small beginnings, the journal has steadily grown, publishing more articles and receiving more recognition from those working in the field. All this is reflected in the news that the journal will this month receive an official impact factor for the first time.

Now, just as a child’s milk teeth must one day be replaced by a larger, more permanent set of adult teeth, so the time has come for BMC Oral Health to move to a new editorial model to ensure it can continue to serve the needs of its community. From this week the journal will be divided up into five sections covering the whole breadth of dental research, each headed by a renowned Section Editor, and supported by a team of Associate Editors drawn from leading researchers from across the world. In addition to benefiting from the research expertise of our new editorial board we look forward to working with them on developing the journal so it keeps abreast of this fast-moving and exciting research field.

Ever since the work of the 18^th century pioneer Pierre Fauchard, ‘the father of modern dentistry’, the need for scientific evaluation of new treatments and tools has been recognised. This is as true today as ever and our Clinical Oral Healthcare Research section, headed by Anton Sculean of Universität Bern in Switzerland, will focus on this important area of research. This section will publish studies evaluating new or existing treatments in a clinical setting, with a particular focus on randomised clinical trials and systematic reviews.

Any treatment that makes it to the clinic will have built on fundamental basic research. Biological diseases are the root cause of many of the most common dental problems and there is an urgent need to know more about the organisms involved. Our Oral Microbiology section, led by Hidenobu Senpuku of the National Institute of Infectious Diseases in Tokyo, will focus on research into the pathology of oral diseases of a biological origin. Equally important is research into new materials and techniques, or the refinement of existing ones. The Dental Techniques: Tools, Materials and Surgical Research section, led by Fausto Mendes of the University of São Paulo in Brazil, will focus on research involving restoration materials and the validation of dental tools.

Even the best treatments are useless if those most in need cannot access them. Evaluating the need for dental treatment and the best way to provide it is more crucial than ever, both in rich countries like the UK and in developing countries where demand for good quality dental care is ever increasing. Our Epidemiology of Oral Health section, headed by Peter Robinson of the University of Sheffield in the UK, will focus on research assessing the social factors determining need for dental care, as well as the environmental, behavioural and occupational correlates of oral health related quality of life. Complementing this research, our Delivery, Management and Promotion of Oral Health and Dental Care section, led by Helen Whelton of University College Cork in Ireland, will publish work on governmental policies affecting dental care, the effectiveness of oral health promotion and the experience of vulnerable groups.

With such a wealth of knowledge now available to draw on, it seems certain that the journal will continue to thrive in the coming years. Of course, as a BMC-Series journal all research will remain freely available for anyone to read and learn from.

To submit your manuscript to BMC Oral Health, please visit the journal website for further information, or contact the Executive Editor Dr Christopher Foote for any pre-submission queries.  We look forward to hearing from you.

Peer review takes time. Sometimes, a lot of time. For many researchers, finding the balance between getting their blood-sweat-and-tears research into a top tier journal, and simply getting it into the literature, can be a maddeningly frustrating process. In fast-paced fields where the risk of being scooped by a rival lab only adds to the pressure, finding that your manuscript is cascading down a list of selective journals is enough to make even the most seasoned professor blanch. Endless cycles of repetitious ...

Read more]]> A new cross-publisher initiative to help make the peer-review process a little less protracted aims to prevent wasted reviewer effort by allowing authors to take their reviewers’ reports to the BMC-series if their manuscript is rejected from eLife.

How portable is your peer-review?

Peer review takes time. Sometimes, a lot of time. For many researchers, finding the balance between getting their blood-sweat-and-tears research into a top tier journal, and simply getting it into the literature, can be a maddeningly frustrating process. In fast-paced fields where the risk of being scooped by a rival lab only adds to the pressure, finding that your manuscript is cascading down a list of selective journals is enough to make even the most seasoned professor blanch. Endless cycles of repetitious re-review, and requests for additional experiments from each successive journal do not make for efficient science, or efficient scientists.

Here in the BMC-series, our aim has always been to help researchers get published – as long their research is deemed a sound, useful addition to the literature by their peers. We do of course recognise that sometimes there can be pressure to publish in more selective journals,  and as a publisher BioMed Central  is equally proud of the achievements of its flagship publications such as BMC Biology, BMC Medicine and Genome Biology, which select the very best in leading edge research in biological and clinical science.

We have for the last decade or so worked closely with our flagship publications to help the transition of manuscripts across these selection thresholds, without unnecessarily wasting peer-review effort. By transferring referee reports alongside manuscripts when they are declined by these selective journals, we hope to provide authors with a simple solution to avoid the vortex of endless review.

The success of this system of portable peer-review has also now been extended across the entire BioMed Central portfolio of journals, to try to make publishing with us that little bit more smooth. This means that any manuscript submitted to BioMed Central can be quickly and easily transferred to any other journal –pre- or post-review—at just the click of button. And the assent of the recipient editor, of course.

A portable feast

Having experienced how well such a system can operate within a large publishing portfolio, we are delighted to now be able to forge cross-publisher links with the latest addition to the stable of high-profile selective journals in biology: eLife. A few weeks ago our sister journal BMC Biology announced that researchers finding themselves rejected from this journal would be offered the opportunity to take their referees reports with them if they wished to continue the peer-review process with our own flagship journal.

Following this announcement, we are very pleased to announce that such an offer would also be welcomed for researchers wishing to publish in any of the subject-specific journals  in the BMC-series too. In many cases, such “post-review” transfers may not even require further review by the same referees: provided that the science is sound and that a full formal response has been provided to the referees comments, consultation with our Editorial Board may be sufficient to convey a swift decision.

Forging the future

In a recent interview with the Economist, BioMed Central’s managing director Matthew Cockerill outlined some of our publishing group’s other initiatives to facilitate smoother peer-review. This included details of recent links forged between our more zoologically-oriented  journals and an innovative new venture called Peerage of Science, that aims to lift the peer-review process out of the hands of publishers completely– until a manuscript is ready to be published.

This, together with similar initiatives such as Rubriq, aims to switch the focus of peer-review from one where researchers are invited to review papers by publishers, to one where researchers actively seek out papers to review. In a publishing climate where reviewer time is being severely squeezed by the volume of requests, it is hoped that this fundamental shift in the way that reviewing operates may lift this burden a little, and perhaps encourage a new generation of researchers to contribute to the scientific review process.

These new cross-publisher—and indeed ex-publisher—links that are now been forged represent a much needed update to the traditional processes of peer-review. And we’re happy to be a part of where they’re headed.

Healthcare: Antibiotic avoidance

Over a third of women presenting with urinary tract infection symptoms are happy to delay antibiotic treatment when asked by their GP, with the majority of these patients showing an improvement in symptoms without the need for further treatment. This intriguingly suggests that patients are much more open to reducing unnecessary antibiotic use than is often thought. More on this study over on our blog.

Microbiology: Conversion of Coccidioides

Coccidioides immitis is a disease-causing fungus ...

Read more]]> Antibiotic avoidance • Conversion of Coccidioides • The geography of mutation • A structural mystery, resolved • Snowflake the albino gorilla • A hidden mechanism of signalling? • Evolution and medicine across Africa • Is it right to recruit by genotype?

Healthcare: Antibiotic avoidance

Over a third of women presenting with urinary tract infection symptoms are happy to delay antibiotic treatment when asked by their GP, with the majority of these patients showing an improvement in symptoms without the need for further treatment. This intriguingly suggests that patients are much more open to reducing unnecessary antibiotic use than is often thought. More on this study over on our blog.

Microbiology: Conversion of Coccidioides

Coccidioides immitis is a disease-causing fungus in mammals that exists as molds in the wild, growing in the desert soils of the southwestern US, and in Central and South America. In humans it can cause Valley Fever or pneumonia through inhalation of spores which eventually turn into pathogenic spherules. Viriyakosol et al. now report that this conversion from spores to spherules requires major transcriptional reprogramming, and has little congruence with genetic mechanisms displayed in other dimorphic fungi.

Cancer: The geography of mutation

A study of the prevalence of genetic mutations in the breast- and ovarian-cancer related genes BRCA1 and BRCA2 in the northern Spanish region of Asturias reveals a number of novel mutations not found in other regions of the country, which may help design a geography-specific screening panel for high-risk breast and/or ovarian cancer families.

Biochemistry: A structural mystery, resolved

Bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain that plays a role in proofreading newly synthesized DNA. However, in E. coli DNA polymerase III the metal-binding residues that underlie this function have been lost, and so the function of this domain is not clear. A new analysis from the Kuriyan lab in UC Berkeley finds that metal binding can be restored with only three point mutations, and that the domain is in fact a major structural element.

Image of the month:

The genome sequencing of Snowflake, the only known albino gorilla, reveals traces of inbreeding. Prado-Martinez et al.

Plant biology: A hidden mechanism of signalling?

Chilli seedlings germinate better when grown in the presence of ‘good neighbour’ plants like basil even when all forms of chemical and visual signals are blocked, suggesting that an as-yet unidentified system of communication exists between plants. National Geographic and Science were listening in.

Genetics:  Evolution and medicine across Africa

Variability in the gene encoding the drug metabolizing enzyme Cytochrome P450 3A5 (CYP3A5) from 36 ethnically diverse populations in Africa reveals that 43% of individuals express this gene, consistent with it playing a role in salt-retention. Lead author of the study Ripudaman K Bains from University College London outlines how understanding our evolutionary past could help guide drug therapies of the future.

Medical ethics: Is it right to recruit by genotype?

A debate article discusses some of the issues surrounding Genotype-Based Recruitment – a study design that allocates clinical trial participants based on their genotypes, rather than clinical conditions. Isabelle Budin-Ljøsne and colleagues suggest that the existing recommendations for recruitment of such studies are not sufficient for a broader use of this design, and highlight the issues that will require more coordinated solutions in the future.

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The rise of antibiotic resistant bacteria poses one of the biggest threats to human health. The UKs chief medical officer, in a report on the threat of increasing bacterial resistance, described it ‘as big a risk as terrorism’.

A number of factors contribute to this problem, such as the lack of financial incentives for drug companies to develop new antibiotics (see Gerard Wright’s recent Q&A article in BMC Biology for more on this), but there is no doubt ...

Read more]]> Women consulting their GP with symptoms of urinary tract infections are often happy to delay antibiotic treatment when their GP requests it. This intriguingly suggests that patients are much more open to reducing unnecessary antibiotic use then is often thought.

The rise of antibiotic resistant bacteria poses one of the biggest threats to human health. The UKs chief medical officer, in a report on the threat of increasing bacterial resistance, described it ‘as big a risk as terrorism’.

A number of factors contribute to this problem, such as the lack of financial incentives for drug companies to develop new antibiotics (see Gerard Wright’s recent Q&A article in BMC Biology for more on this), but there is no doubt that the biggest reason is the misuse and overuse of antibiotics. In some countries (especially in the developing world) antibiotics are available ‘over the counter’ without a prescription, inevitably leading to their indiscriminate use. However even in countries where antibiotics are only available from a doctor, over-prescribing and unnecessary use are still all too common.

This raises the question of who is responsible for this over-prescribing – the doctor, or the patient? The general consensus is that patients are mostly to blame (see here for an example); they demand access to antibiotics even when advised against this by their physician, placing doctors under pressure to prescribe the drugs even when they think it unnecessary.

It was this assumption that a new study, published today in BMC Family Practice, set out to test. Carried out by Bart Knottnerus and colleagues at the University of Amsterdam, the study tested women’s willingness to delay antibiotic use when consulting their doctor with symptoms of urinary tract infections.

Urinary tract infections (UTIs) are a good focus for this type of study. A common condition in women, it is not a serious infection, but symptoms are bothersome and can reduce quality of life. Guidelines often recommend immediate treatment with antibiotics for any patient presenting with UTI symptoms. However, past studies have shown that in 25-50% of women symptoms will disappear by themselves within a week. This then, seems to be a textbook case of antibiotic overuse; patients, many of whom will recover without treatment, being prescribed antibiotics regardless. The question then: is it true that patients with UTI symptoms expect and demand treatment with antibiotics?

To find the answer, Knottnerus and colleagues recruited a number of General Practitioners (GPs) in the Amsterdam region to take part in their study. They requested that these GPs ask patients presenting with typical UTI symptoms to delay antibiotic treatment for one week; more than a third of patients were prepared to do so. Over 70% of patients delaying treatment had improved symptoms after a week; that it to say, prescribing antibiotics to these women would have been unnecessary and wasteful.

These results suggest that the common perception that patients demand immediate treatment is not always correct. Instead, perhaps it is this perception among doctors that is sometimes to blame for unnecessary antibiotic prescriptions. It is notable that one of the doctors recruited into this study refused, as a point of principle, to ask his patients to delay treatment. Might results from studies such as this encourage GPs to be a bit more trusting of their patients when it comes to using antibiotics responsibly?

Of course one should not overstate these results. After all, almost two thirds of women preferred to begin treatment immediately, even when the reasons why a short delay might be beneficial were explained by their doctor. In addition, almost half of the women who initially agreed to delay treatment did in fact use antibiotics before the week was out; evidently some patients will feel the need for immediate relief from their uncomfortable symptoms, even when they appreciate the good reasons why they should delay treatment.

Even with these caveats, there is no doubt that this study makes an important contribution to the debate on reducing unnecessary use of antibiotics. Perhaps one of the biggest contributions GPs can make is to put a bit more trust in their patients to do the right thing.

BMC International Health and Human Rights announces a call for submissions to a thematic series on health policy and systems in emerging economies. The “emerging economies” are fast growing and changing societies. They are the BRIC countries (Brazil, Russia, India, and China) that make up over 40 percent of the world’s population as well as other successful economies including Indonesia, Vietnam, Chile, Colombia, Mexico, Nigeria, South Africa, Turkey and South Korea. Such countries face important questions about how best to promote equitable and inclusive development – domestically, regionally and globally. The aim of this thematic series is to explore the challenges of creating policies for health in these settings.

We welcome submissions regarding all aspects of health policy and ...

Read more]]>

BMC International Health and Human Rights announces a call for submissions to a thematic series on health policy and systems in emerging economies. The “emerging economies” are fast growing and changing societies. They are the BRIC countries (Brazil, Russia, India, and China) that make up over 40 percent of the world’s population as well as other successful economies including Indonesia, Vietnam, Chile, Colombia, Mexico, Nigeria, South Africa, Turkey and South Korea. Such countries face important questions about how best to promote equitable and inclusive development – domestically, regionally and globally. The aim of this thematic series is to explore the challenges of creating policies for health in these settings.

We welcome submissions regarding all aspects of health policy and systems in emerging economies that illuminate relationships between economic development and health and human rights, including, but not limited to, the following topics:

• social protection floors, universal healthcare and social guarantees
• the ‘new middle classes’ and health policy
• finance capital and commercial activity in healthcare
• environment and health
• preventive health policy
• law and governance challenges
• trade in health services and other transnational mobilities
• health-related aid
• policy innovations offering lessons for health policy in poorer nations and regions

Literature reviews, comparative studies and single case studies are welcomed. We encourage you to submit your original articles by August 31, 2013. To submit your manuscript, please use our online submission system and indicate in your cover letter that you would like the manuscript to be considered for the ‘health policy and systems in emerging economies’ thematic series.

A special 20% discount off the Article Processing Charge (APC) will be granted to all accepted manuscripts submitted by July 31, 2013 (please mention waiver code IHHRTHEM). All manuscripts will undergo peer review according to the journal’s policy.

Please contact the BMC International Health and Human Rights editorial team if you have questions regarding the suitability of your paper for this series.

Susan F. Murray,
Guest Editor

Irene Pala,
Executive Editor

Emily Crow,
Executive Editor

Caravaggio is not an artist traditionally associated with Berlin, but discussion of potential causes of his death–postulated to be due to sepsis– at a recent microbiology conference held in the city–mean that sometime in future  he just may be! Luckily the eventful  life of the famous Italian painter was not emulated by the participants at the 23rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2013) and we, BMC Infectious Diseases included, instead enjoyed a diverse set of presentations covering the whole spectrum of infectious disease research.

The focus of many of the talks was on prevention, rather than the treatment of diseases, from Linos Vandekerckhove’s review of early initiation of HIV treatment to prevent transmission, ...

Read more]]>

Thomas Wolf/Wikipedia

Caravaggio is not an artist traditionally associated with Berlin, but discussion of potential causes of his death–postulated to be due to sepsis– at a recent microbiology conference held in the city–mean that sometime in future  he just may be! Luckily the eventful  life of the famous Italian painter was not emulated by the participants at the 23^rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2013) and we, BMC Infectious Diseases included, instead enjoyed a diverse set of presentations covering the whole spectrum of infectious disease research.

The focus of many of the talks was on prevention, rather than the treatment of diseases, from Linos Vandekerckhove’s review of early initiation of HIV treatment to prevent transmission, to the debate between Didier Pittet and Marc J.M. Bonten on the most effective measure to prevent hospital-acquired infections. Even humble bed linen was investigated and found, at times, wanting in a talk by Michelle Balm discussing an outbreak of Bacillus cereuscaused by a combination of construction work and laundry practices.

James Heilman, MD/Wikipedia

The difficulties in performing studies on interventions, such as hand hygiene compliance, and the lack of data on which to test these theories was discussed and several pleas were made to remember that sometimes common sense is just as important as trial data (with reference to this systematic review on parachutes).

This year also featured more clinical parasitology, with insights into artesunate treatment for severe malaria by Peter Kremsner, and Paul Newton’s fascinating discussion on counterfeit anti-malarials (more detailed information on this can be found here). In addition, the spread of artemisinin drug resistance at the resistance hotspot at Thailand’s borders was also highlighted by François Nosten.

From parasites to viruses with a series of talks on the role, or potential role, of cytomegalovirus in a series of diseases such as inflammatory bowel disease and cancer. At present much of this data is in early stages, but talks from Carlos Lumbreras on the potential link with inflammatory bowel disease, and from Cecilia Soderberg-Naucler, using data from her trials on CMV treatment in patients with glioblastoma, showed that this is an area that will continue to be investigated.

And finally back to paleomicrobiology with a report of a possible mycobacterium infection in La Doncella, a 500 year old Inca mummy found on Llullaillaco in Argentina by Angelique Corthals. Although the challenges we face in tackling infectious diseases in 2013 are different to our ancestors, it’s clear there is a long way still to go. Hopefully ECCMID2014  will continue to point us in the right direction.

Translational research in ophthalmology is a fast growing field, with many centers now having dedicated groups focussing on bench to bedside approaches to research. There have been many recent major advances in the fields of cell biology, biochemistry and elsewhere, for example in stem cell research and nanotechnology based drug delivery systems. This means that multidisciplinary research projects looking to allow these novel technological advances to make a real difference to disease outcomes in a clinical setting is more important than ever.

In order to provide a dedicated home for this exciting translational research BMC Ophthalmology is launching a new article collection entitled Translational Ophthalmology: Looking to the future. The collection particularly encourages submission ...

Read more]]> By Emilie Aimé, Executive Editor BMC Ophthalmology

Translational research in ophthalmology is a fast growing field, with many centers now having dedicated groups focussing on bench to bedside approaches to research. There have been many recent major advances in the fields of cell biology, biochemistry and elsewhere, for example in stem cell research and nanotechnology based drug delivery systems. This means that multidisciplinary research projects looking to allow these novel technological advances to make a real difference to disease outcomes in a clinical setting is more important than ever.

In order to provide a dedicated home for this exciting translational research BMC Ophthalmology is launching a new article collection entitled Translational Ophthalmology: Looking to the future. The collection particularly encourages submission of translational research that focuses on improving disease outcomes.

An interesting and timely review of systemic therapies for inflammatory eye disease by Alastair Denniston and Andrew Dick was recently published in the journal.

Systemic therapies for inflammatory eye disease: Past, Present and Future
Alastair K Denniston, Andrew D Dick
BMC Ophthalmology 2013, 13:18

We welcome research submissions for the article collection to any section of BMC Ophthalmology.

If your organization is a BioMed Central Member, the cost of the article processing charge is covered in full or in part by the Membership.

P.S. Come and meet the journal’s Executive Editor at ARVO 2013 – email emilie.aime@biomedcentral.com to arrange a meeting

One of the most significant accomplishments of the genomics revolution has been an improvement in our understanding of why certain populations have elevated risks for developing specific diseases. ...

Read more]]> It is now well established that different human populations may exhibit very different responses to therapeutic drugs. However, to what extent this may have been influenced by our evolutionary history is less well known. In this guest blog, Ripudaman K Bains from University College London outlines why understanding our past can help inform our future, and describes her recent work published in BMC Genetics with colleagues from Addis Ababa University, Henry Stewart Group and Uppsala University on molecular diversity and population structure at the Cytochrome P450 3A5 gene in Africa.

One of the most significant accomplishments of the genomics revolution has been an improvement in our understanding of why certain populations have elevated risks for developing specific diseases. It has enabled us to examine diversity across multiple and previously uncharacterized human populations and improved our understanding of human genetic diversity across geographic regions, ultimately helping  us to identify the evolutionary processes that have shaped population differences.  There are now well-established ethnic and population differences in the genetic predisposition to certain diseases; for example the higher risk of Tay-Sachs disease in Ashkenazi Jewish populations (1, 2) and the high proportion of blood disorders in populations from malaria endemic regions, such as glucose-6-phosphate dehydrogenase deficiency (3) and sickle cell disorder (4, 5).

Genetic variability does not only influence disease phenotype and pathology; it can also influence the safety and efficacy of drug treatment. As such, the results of drug therapy can vary within and between populations. Most patients respond well to drug treatment at standardized dosages, however there are individuals who have minimal or no therapeutic response. Additionally, some patients experience severe adverse drug reactions, which are major contributors to global morbidity and mortality. Once a drug is administered, it is absorbed and distributed to the site of action, where it interacts with targets such as receptors or enzymes. Most drugs undergo metabolism before being excreted. Genetic variation may affect absorption, enzyme activity, cellular uptake, and metabolism, resulting in altered drug activity or half-life. Variation in genes encoding drug metabolizing enzymes, such as those in the Cytochrome P450 (CYP450) super-family, can contribute to sub-optimal clinical outcomes.

Tailored therapy

The clinical vision for studies of genes encoding drug metabolizing enzymes is that genetic variation identified within these genes may one day be used to tailor drug therapies based on an individual’s genotype. However, the implementation of genotype-guided medicine for individuals is not currently in widespread clinical use. Physicians are becoming increasingly aware of clinically relevant genetic polymorphisms. However, a 2006 study by the Federal Drug Administration reported that only ~25% of all prescriptions written in the USA contained pharmacogenetics labeling. The paucity of affordable and efficient testing methods, in addition to the continuous identification of clinically important genetic variants, has delayed the translation of human genetic information into clinical practice and healthcare administration. Population-based studies can go some way towards filling this gap. Studying the distribution of pharmacogenetically relevant variants among populations, instead of individuals, has identified common, medically important, variation. However there are many populations, particularly within Africa, that remain under-represented in population pharmacogenetics studies.

The importance of including African populations within evolutionary and clinical research should not be underestimated. The majority of archaeological and genetic data support a recent African origin model of the evolution of anatomically modern humans ~150,000-200,000 years ago. As a result Africa has extensive inter-ethnic genetic diversity, in addition to considerable inter-ethnic cultural, phenotypic and linguistic differences. From a medical perspective, there are marked differences between African populations and European populations in the response to specific treatments that are administered for diseases. However, over 95% of drug development and clinical trials are carried out in European and North American populations, both with predominantly recent European ancestry. Many developing countries, including those in Africa, rely on FDA and European guidelines for safety levels and optimal therapeutic dosages. There are few large-scale studies examining variation in drug metabolizing enzymes across multiple, geographically and ethnically diverse African populations.

In our recent BMC Genetics publication we attempted to address this imbalance. We used a multi-disciplinary approach to characterize and analyze intra-African variation at the gene encoding the drug metabolizing enzyme Cytochrome P450 3A5 (CYP3A5), which is involved in the metabolism of ~50% of all clinically administered drugs. However, CYP3A5 is variably expressed; individuals tend to express the protein at high concentrations or have low to undetectable levels of protein. In addition to being the largest study, to date, of CYP3A5 variation in Africa, our approach differs from previous studies in that we used molecular and evolutionary approaches to understand population-level variation in the CYP3A5 gene. Our study found that CYP3A5 is likely to be one of the most pharmacologically active drug metabolizing enzymes in Africa. Our estimate of the proportion of individuals across Africa who express CYP3A5 (43%) is considerably lower than previous, independent estimates from the continent (55-95%). This is considerably higher than independent estimates for individuals with recent European ancestry (10%), Asian (25%) and South American (30%) populations. Our findings suggest that there are likely to be multiple pharmacogenetics profiles, relating to variable CYP3A5 expression, across different African populations.

Evolutionary medicine

We also examined population differences in the frequencies of functional variation at the CYP3A5 gene in an evolutionary context. CYP450 genes are largely studied for their role in drug and hormone metabolism. However, the ability of these enzymes to metabolize drugs is a by-product of what is believed to be their “native” role, since CYP450 paralogues exist in multiple prokaryotic and eukaryotic species, and the genes are thought to have existed on the planet for over 2 billion years. It is thought that the ability of CYP450 enzymes to metabolize exogenous compounds evolved 400-500 million years ago to enable animals to digest certain toxic chemicals found in plants, creating water-soluble compounds which are easier to excrete. Their role as drug metabolizing enzymes has arrived very late in human evolutionary history.

The application of evolutionary principles to medical research – the emerging field of “evolutionary medicine” – attempts to understand how environmental and genetic factors have shaped our vulnerabilities and responses to diseases and therapies throughout human evolutionary history. We attempted to identify environmental factors which may predict CYP3A5 expression patterns across global regions, and infer evolutionary factors which may have shaped the observed correlations. CYP3A5 is involved in the metabolism of renal cortisol to 6-β-hydroxycortisol, a key regulator of renal sodium transport. From an evolutionary perspective, salt and water retention are vital traits in populations that frequently experience water shortages. A previous study reported that equatorial populations, which are most vulnerable to water shortages, were much more likely to express CYP3A5 at high concentrations. Within these regions, rapid salt and water retention should provide an evolutionary advantage.

We examined this further by testing for correlations between CYP3A5 expression phenotypes and ecological data relating to aridity for the present day, the Holocene (the last ~10,000 years) and the Late Pleistocene (~50,000 to ~10,000 years ago) periods. We found significant gene-environment interactions, which show that individuals living in dry and arid environments are more likely to express CYP3A5. Interestingly, we found significant correlations between high CYP3A5 expression phenotypes and aridity data from the Holocene and Late Pleistocene. This was also seen for temperature data for each time period. Our findings provide further support for a hypothesis that the CYP3A5 enzyme may have been involved in salt retention and heat adaptation, which explains some of the differences in CYP3A5 expression patterns that we observed across Africa.

There remains a need for focused studies to establish the relationship between environmental variables, patterns of genetic variation, and clinical outcomes within Africa. This is not limited to studies of CYP450 genes; detailed studies of additional drug metabolizing genes, and genetic markers important in predicting clinical outcomes, will become increasingly necessary as we move towards the era of personalized genomics.

1.    Myerowitz R; The search for the genetic lesion in Ashkenazi Jews with Classic Tay-Sachs disease. Adv Genet 2001;44:137-43.
2.    Frisch A, Colombo R, Michaelovsky E, et al.; Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis. Hum Genet 2004;114(4):366-76. doi: 10.1007/s00439-003-1072-8.
3.    Tishkoff SA, Varkonyi R, Cahinhinan N, et al.; Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 2001;293(5529):455-62. doi: 10.1126/science.1061573
4.    Mabayoje JO; Sickle-cell anaemia; a major disease in West Africa. Br Med J 1956;1(4960):194-6.
5.    Trowell HC, Raper AB, Welbourn HF; The natural history of homozygous sickle-cell anaemia in Central Africa. Q J Med 1957;26(104):401-22.

Explore more on developments in evolutionary medicine in this article collection from BMC Medicine: Evolutionary Medicine : clinical medicine from an evolutionary perspective

BMC Ophthalmology is excited to be going to this year’s ARVO meeting. 2013 sees the annual ARVO conference stopping in Seattle, home of grunge, that famous high street coffee chain and for one week only BMC Ophthalmology. We are looking forward to a diverse range of talks and would be happy to meet you there. If you are attending and would like to discuss anything please contact Executive Editor Emilie Aimé