Association between polymorphisms in the β2-adrenergic receptor gene with myocardial infarction and ischaemic stroke in women

Results from studies investigating the association between polymorphisms in the beta 2-adrenergic receptor gene (ADRB2) and cardiovascular disease (CVD) are controversial. Using haplotype-based analysis, we have previously shown a protective effect of the Gly16-Gin27-Ile164 haplotype on myocardial infarction in men. We sought to replicate these findings in women and further investigated whether the gene variants exert differential effects on myocardial infarction and ischaemic stroke. We performed a prospective study among 25,224 women, participating in the Women's Health Study and free of CVD at study entry. We had information on polymorphisms Gly16Arg, Gln27Glu, and Thr164Ile in the ADRB2. Incident CVD was self-reported and confirmed after medical record review. We used proportional hazards models to investigate the association between genotypes and haplotypes with any myocardial infarction, any ischaemic stroke, and CVD death. During a mean of 11.8 years of follow-up, 274 myocardial infarctions, 299 ischaemic strokes,and 159 CVD deaths occurred. Among the whole cohort genotype- and haplotype-based analyses did not show an association for any of the gene variants with any of the CVD outcomes. When we focused on Caucasian women, the haplotype-based analysis, however, suggested an inverse association of the haplotype Gly16-Gln27-Thr164 with incident myocardial infarction (multivariable-adjusted hazard ratio 0.75; 95% confidence interval 0.58-0.97; p=0.03). We did not find associations in the haplotype-based analyses with incident ischaemic stroke or CVD death. Our results suggest that the haplotype Gly16-Gln27-Thr164 is associated with reduced risk of incident myocardial infarction but not ischaemic stroke in Caucasian women and suggest differential pathophysiologies for myocardial infarction and stroke.