Relationships between common polymorphisms of adenosine triphosphate-binding cassette transporter A1 and high-density lipoprotein cholesterol and coronary heart disease in a population with type 2 diabetes mellitus.
Patients with type 2 diabetes mellitus (T2D) have a high coronary risk partly because of low levels of high-density lipoprotein-cholesterol (HDL-C). The adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays a key role in HDL metabolism. We studied the association of common single nucleotide polymorphisms (SNPs) in the ABCA1 gene with HDL-C levels and coronary risk in a cohort of subjects with T2D. We studied 5 SNPs: +69C>T, +378G>C, R219K, I883M, and R1587K. The C allele of +378G>C was significantly associated with lower HDL-C concentrations (P = .04); and the M allele of I883M, with higher HDL-C concentrations (P = .03). No significant association was found between these SNPs and the incidence of new coronary events. Nevertheless, cross-sectional data on entry showed that the frequency of K219 was lower in patients with previous coronary heart disease (angina pectoris and/or myocardial infarction) (odds ratio, OR [95% confidence interval, CI] = 0.80 [0.65-0.98], P = .03, after adjustment for multiple risk factors other than HDL-C). The frequency of K1587 was higher in patients with angina pectoris (OR [95% CI] = 1.27 [1.01-1.58], P = .04, after multiple adjustment). The TT genotype of the C69T SNP was less frequent in subjects with prior myocardial infarction (OR [95% CI] = 0.28 [0.13-0.61], P = .001, after multiple adjustment). These associations persisted after further adjustment for HDL-C levels. In conclusion, common genetic variations of ABCA1 had a moderate influence on HDL-C levels and/or coronary heart disease in patients with T2D. These 2 effects were independent.
Porchay-Baldérelli
Isabelle
I
INSERM U695, Genetic Determinants for Type 2 Diabetes and its Vascular Complications, Xavier Bichat Medical School, 16 rue Henri Huchard, 75018 Paris, France.
Péan
Franck
F
Emery
Nathalie
N
Maimaitiming
Suliya
S
Bellili
Naima
N
Travert
Florence
F
Mohammedi
Kamel
K
Roussel
Ronan
R
Marre
Michel
M
Fumeron
Frédéric
F
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000150:complications / Q000235:genetics*; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D004247:DNA