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

• Published in: Atherosclerosis Vol. 204; no. 1; pp. 165 - 170
• Main Authors: IZAR, Maria C, HELFENSTEIN, Tatiana, BODANESE, Luis C, MORIGUCHI, Emilio H, SARAIVA, Jose F, INTROCASO, Luiz, SOUZA, Agnaldo D, SCARTEZINI, Marileia, TORRES, Kerginaldo P, ZAGURY, Leao, JARDIM, Paulo C, COSTA, Eduardo A, IHARA, Silvia S, TACITO, Lucia H, FORTI, Adriana, MAGALHAES, Maria E, CHACRA, Antonio R, BERTOLAMI, Marcelo C, LOURES-VALE, Andreia A, BARROS, Marco A, XAVIER, Hermes T, LYRA, Ruy, ARGAMANIJAN, Dikran, RELVAS, Waldir G, GUIMARAES, Armenio, NOVAZZI, Jose P, KASINSKI, Nelson, AFIUNE, Abrahao, MARTINEZ, Tania L, SANTOS, Raul D, NICOLAU, Jose C, CESAR, Luiz A, POVOA, Rui M, CARVALHO, Antonio C, SANTOS, Andreza O, HAN, Sang W, FONSECA, Francisco A, FISCHER, Simone C, PINTO, Leonor E, LOPES, Ieda E, POMARO, Daniel R, FONSECA, Marilia I
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.05.2009
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Brazil; Cardiology. Vascular system; Case-Control Studies; Coronary heart disease; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Frequency; Genetic Predisposition to Disease; Heart; Humans; Lipids - blood; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Logistic Models; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - enzymology; Myocardial Infarction - genetics; Odds Ratio; Phenotype; Polymorphism, Genetic; Prospective Studies; Risk Assessment; Risk Factors; Brazil; Endocrinopathy; Type 2 diabetes; Myocardial infarction; Metabolic diseases; Cardiovascular disease; Lipids; Lipoprotein lipase; Apolipoproteins; Polymorphisms; Coronary heart disease; Myocardial disease; Genetic determinism; Risk factor; Genetics; Diabetes; Polymorphism
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2008.08.006

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 (epsilon2, epsilon3, epsilon4,), 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.