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

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) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (ɛ2, ɛ3, ɛ4,), PON-1 (Q192R), and two LCAT variants Arg147 → Trp and Tyr171 → 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.