Clinical Chemistry
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Clinical Chemistry 54: 1183-1189, 2008. First published May 16, 2008; 10.1373/clinchem.2007.102400
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(Clinical Chemistry. 2008;54:1183-1189.)
© 2008 American Association for Clinical Chemistry, Inc.

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Association between ESR2 Genetic Variants and Risk of Myocardial Infarction

Sophie Domingues-Montanari1, Isaac Subirana1, Marta Tomás1, Jaume Marrugat1,2 and Mariano Sentí1,3,a

1 Unitat de Lípids i Epidemiologia Cardiovascular, Institut Municipal d’Investigació Mèdica (IMIM), Barcelona, Spain; 2 Universitat Autònoma de Barcelona, Barcelona, Spain; 3 Universitat Pompeu Fabra, Barcelona, Spain.

aAddress correspondence to this author at: Unitat de Lípids i Epidemiologia Cardiovascular, Institut Municipal d’Investigació Mèdica, c/ Dr Aiguader 88, Barcelona 08003, Spain. E-mail msenti{at}imim.es.

Background: Environmental and genetic factors contribute to the development of complex diseases such as myocardial infarction (MI), the leading cause of death in men and women. Women develop MI approximately 10 years later than men, a difference that could be explained by the genes coding for the estrogen receptors. Single nucleotide polymorphisms (SNPs) in the ESR2 gene may affect susceptibility for MI in a sex-dependent manner.

Methods: A nested case-control design was used to analyze 3 polymorphisms of the ESR2 gene and their associated haplotypes in 710 myocardial infarction cases from the REGICOR (Registre Gironí del Corazón) study and 2379 controls randomly selected in a representative population of a Spanish cross-sectional study.

Results: The rs1271572 T allele was significantly more common in patients who developed MI (P < 0.001). No association was observed for rs1256049 or rs4986938. Assuming a dominant model of inheritance, the association, as determined by logistic multivariate regression after adjustment for conventional cardiac risk factors, remained statistically significant in men [odds ratio (OR) 1.65, 95% CI 1.18–2.30; P = 0.003) but not in women (P = 0.754). A very common haplotype encompassing the rs1271572 variant was also associated with the risk of MI in the overall population (OR 1.41, 95% CI 1.06–1.87; P = 0.020) and in men (OR 1.57, 95% CI 1.12–2.21; P = 0.009).

Conclusions: The rs1271572 SNP T variant was associated with increased risk of MI in a Spanish population, and this association was found to be limited to men only. Sex differences in the genetic risk merit further investigation.






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