title: Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.
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.
authors.affiliation: Cardiology Division, Department of Medicine, Rua Pedro de Toledo 276, São Paulo, SP, Brazil. mcoizar@terra.com.br
authors.forename: Maria C
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authors.lastname: Izar
authors.forename: Tatiana
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authors.lastname: Helfenstein
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authors.lastname: Magalhaes
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authors.initials: AR
authors.lastname: Chacra
authors.forename: Marcelo C
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authors.lastname: Bertolami
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authors.initials: AA
authors.lastname: Loures-Vale
authors.forename: Marco A
authors.initials: MA
authors.lastname: Barros
authors.forename: Hermes T
authors.initials: HT
authors.lastname: Xavier
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authors.lastname: Lyra
authors.forename: Dikran
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authors.lastname: Argamanijan
authors.forename: Armenio
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authors.lastname: Guimaraes
authors.forename: Jose P
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authors.lastname: Novazzi
authors.forename: Nelson
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authors.lastname: Kasinski
authors.forename: Abrahao
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authors.lastname: Afiune
authors.forename: Tania L
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authors.lastname: Martinez
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.forename: Jose C
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authors.lastname: Nicolau
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Cesar
authors.forename: Rui M
authors.initials: RM
authors.lastname: Povoa
authors.forename: Antonio C
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authors.lastname: Carvalho
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D008055:Lipids; D008071:Lipoprotein Lipase