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 (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.
Izar
Maria C
MC
Cardiology Division, Department of Medicine, Rua Pedro de Toledo 276, São Paulo, SP, Brazil. mcoizar@terra.com.br
Helfenstein
Tatiana
T
Ihara
Silvia S
SS
Relvas
Waldir G
WG
Santos
Andreza O
AO
Fischer
Simone C
SC
Pinto
Leonor E
LE
Lopes
Ieda E
IE
Pomaro
Daniel R
DR
Fonseca
Marilia I
MI
Bodanese
Luis C
LC
Moriguchi
Emilio H
EH
Saraiva
Jose F
JF
Introcaso
Luiz
L
Souza
Agnaldo D
AD
Scartezini
Marileia
M
Torres
Kerginaldo P
KP
Zagury
Leao
L
Jardim
Paulo C
PC
Costa
Eduardo A
EA
Tacito
Lucia H
LH
Forti
Adriana
A
Magalhaes
Maria E
ME
Chacra
Antonio R
AR
Bertolami
Marcelo C
MC
Loures-Vale
Andreia A
AA
Barros
Marco A
MA
Xavier
Hermes T
HT
Lyra
Ruy
R
Argamanijan
Dikran
D
Guimaraes
Armenio
A
Novazzi
Jose P
JP
Kasinski
Nelson
N
Afiune
Abrahao
A
Martinez
Tania L
TL
Santos
Raul D
RD
Nicolau
Jose C
JC
Cesar
Luiz A
LA
Povoa
Rui M
RM
Carvalho
Antonio C
AC
Han
Sang W
SW
Fonseca
Francisco A
FA
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
D008055:Lipids; D008071:Lipoprotein Lipase