Qualitative assessment of previous evidence and an updated meta-analysis confirms lack of association between the ESR1 rs2234693 (PvuII) variant and coronary heart disease in men and women

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Abstract

Background: Coronary heart disease (CHD) is the leading cause of mortality worldwide. CHD clusters in families but this familial aggregation remains largely unexplained. ESR1 is a candidate gene for CHD although recent meta-analyses of the rs2234693 variant reported inconsistent evidence for association with myocardial infarction (MI) in men. The objectives of this study were to perform a qualitative and a quantitative assessment of all evidence to date regarding this association. Methods: We performed structured literature searches for studies addressing the association between the ESR1 rs2234693 and CHD. We assessed the quality of these studies collectively and individually according to recently published guidelines on the reporting and interpretation of genetic association studies. We also performed a meta-analysis of all studies to date, including a sample of MI cases and controls from our region. Results: The qualitative assessment indicated that many studies met a low proportion of the criteria proposed by the current guidelines. No significant association between ESR1 rs2234693 and MI was observed in our sample or in the meta-analysis (16 studies; N ∼ 32,000; OR ∼ 1). Strong between-study heterogeneity was largely explained by a quality score based on the quality criteria. Studies that reported significant associations were generally of poorer quality. Conclusion: We confirm the lack of association between the ESR1 rs223469 and CHD, and show that inconsistencies between previous studies is explained by differences in their quality. © 2009 Elsevier Ireland Ltd. All rights reserved.

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Lluís-Ganella, C., Lucas, G., Subirana, I., Escurriol, V., Tomás, M., Sentí, M., … Elosua, R. (2009). Qualitative assessment of previous evidence and an updated meta-analysis confirms lack of association between the ESR1 rs2234693 (PvuII) variant and coronary heart disease in men and women. Atherosclerosis, 207(2), 480–486. https://doi.org/10.1016/j.atherosclerosis.2009.05.038

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