Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes The genetics, outcomes, and lipids in type 2 diabetes (GOLD) study

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Izar‚ M.C. ; Helfenstein‚ T. ; Ihara‚ S.S. ; Relvas‚ W.G. ; Santos‚ A.O. ; Fischer‚ S.C. ; Pinto‚ L.E. ; Lopes‚ I.E. ; Pomaro‚ D.R. ; Fonseca‚ M.I. ; others

• Document type: Journal article
• Source: ATHEROSCLEROSIS; v. 204, n. 1, p. 165-170, 2009.
• Web of Science Citations: 18

Abstract

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n = 386). or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n = 604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) noncoding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon 2, epsilon 3, epsilon 4,), PON-1 (Q192R), and two LCAT variants Arg(147) -> Trp and Tyr(171) -> Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs. 12%, p = 0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI = 1.79-3.39, p < 0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR = 1.50,95% CI = 1.02-2.25, p = 0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes. (C) 2008 Elsevier Ireland Ltd. All rights reserved. (AU)