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) 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.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Lipids/blood , Lipoprotein Lipase/genetics , Myocardial Infarction/genetics , Polymorphism, Genetic , Adult , Aged , Aged, 80 and over , Brazil , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/enzymology , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Lipoprotein Lipase/metabolism , Logistic Models , Male , Middle Aged , Myocardial Infarction/blood , Myocardial Infarction/enzymology , Odds Ratio , Phenotype , Prospective Studies , Risk Assessment , Risk FactorsABSTRACT
A aterosclerose é a principal causa de síndromes coronarianas agudas, como a angina instável e o infarto do miocárdio. A despeito de considerável avanço no tratamento agudo e também em relação a sua estratificação, as síndromes coronarianas agudas permanecem como a causa mais comum de morte no mundo industrializado. Recentemente, o uso de estatinas foi capaz de modificar a evolução de eventos coronarianos se iniciado precocemente após a síndrome coronariana aguda. A despeito da riqueza de evidências a partir dos clássicos estudos de prevenção secundária, como 4S, LIPID e CARE, demonstrando a eficiência das estatinas, essas drogas são ainda subutilizadas. Atualmente, considerável quantidade de evidência em relação a efeitos pleiotrópicos tem sido relatada, estendendo o uso dessas drogas além da redução lipídica. Assim, reduzindo o risco trombótico, melhorando a função endotelial e diminuindo a inflamação, as estatinas são capazes de modificar a história natural da doença arterial coronariana.
