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

• Published in: Metabolism, clinical and experimental clinical and experimental, 2009, Vol.58 (1), p.74-79
• Main Authors: Porchay-Baldérelli, Isabelle, Péan, Franck, Emery, Nathalie, Maimaitiming, Suliya, Bellili, Naima, Travert, Florence, Mohammedi, Kamel, Roussel, Ronan, Marre, Michel, Fumeron, Frédéric
• Format: Article
• Language: English
• Subjects: Aged; Alleles; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Cholesterol, HDL - blood; Cohort Studies; Coronary Disease - blood; Coronary Disease - complications; Coronary Disease - genetics; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; DNA - chemistry; DNA - genetics; Endocrinology & Metabolism; Female; Genotype; Humans; Logistic Models; Male; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prevalence; Prospective Studies; Randomized Controlled Trials as Topic
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2008.08.009

Abstract 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.