No replication of association between estrogen receptor α gene polymorphisms and susceptibility to myocardial infarction in a large sample of patients of European descent

Background-The effects of estrogen on blood vessels are partly due to changes in vascular cell gene expression and protein synthesis that are mediated by estrogen receptors. In previous association studies, the -397T/C ( rs2234693) and -351A/G (rs9340799) single nucleotide polymorphisms in the estrogen receptor alpha gene ( ESR1) have been implicated in the risk of coronary atherosclerosis and myocardial infarction. To test these findings, we examined the relationship of the polymorphisms to myocardial infarction in a large sample of white patients and control individuals of predominantly European descent. Methods and Results-The case group included 3657 patients with myocardial infarction, and the control group comprised 1211 individuals with angiographically normal coronary arteries and without signs or symptoms of myocardial infarction. TaqMan assays were used for the determination of genotypes. Genotype distributions of the -397T/ C and -351A/G polymorphisms were not significantly different between the control and patient groups ( P >= 0.85). The frequencies of haplotypes defined by the -397T/ C and -351A/ G polymorphisms were similar in the control group and the patient group ( P = 0.42). In addition, the distributions of haplotype-defined genotypes (diplotypes) were not significantly different between the control group and the patient group ( P = 0.81). Separate analyses in women and men did not reveal sex-related associations of specific genotypes or haplotypes of the polymorphisms with myocardial infarction ( P >= 0.25). Conclusions - The results indicate that the -397T/C and -351A/G polymorphisms of ESR1 or haplotypes based on these polymorphisms are not associated with myocardial infarction in a white population.