Debates
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
second study.

A team led byRoss Prenticefrom theFred
Hutchinson Cancer Research Centerin Seattlenow reports inGenome Medicinetwo 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 theWomen’s Health Initiativeclinical trial and developed a two-step
process to examine potential genetic variants (single nucleotide polymorphisms
or SNPs). The first stage of theprocedure
involved screening2763SNPs frompreviously 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 withstroke risk.

The team found two SNPs in theF13A1
region and two SNPs in thePCSK9region that interact with hormone
therapy on stroke risk.

Of
particular interest is thePCSK9region;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
thePCSK9gene an interesting
candidate gene to explore further.