rage over why multiple large-scale studies to uncover risk factors for stroke have
so far explained only a tiny proportion of inherited stroke cases and why, as
yet, no single genomic region identified in one study has been validated in a
A team led by Ross Prentice from the Fred
Hutchinson Cancer Research Center in Seattle now reports in Genome Medicine two genomic regions that are linked to
stroke risk in post-menopausal women taking hormone therapy. They used a new
approach designed to uncover environmental effects, in this case the hormones
estrogen and progesterone, that interact with genetic effects.
They used data from the Women’s Health Initiative clinical trial and developed a two-step
process to examine potential genetic variants (single nucleotide polymorphisms
or SNPs). The first stage of the procedure
involved screening 2763 SNPs from previously published studies to identify the
subset having nominally significant associations with stroke risk. In the subsequent
stage the authors used this information to look for SNPs involved in hormone
therapy interaction with stroke risk.
The team found two SNPs in the F13A1
region and two SNPs in the PCSK9 region that interact with hormone
therapy on stroke risk.
particular interest is the PCSK9 region; previous studies have reported an
increase in the protein PCSK9 in blood following estrogen-only hormone
treatment. This new association of PCSK9 with increased risk of stroke makes
the PCSK9 gene an interesting
candidate gene to explore further.