Relationships between common polymorphisms of adenosine triphosphate-binding cassette transporter Al and high-density lipoprotein cholesterol and coronary heart disease in a population with type 2 diabetes mellitus
Abstrakt
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 Al (ABCAl) plays a key role in HDL metabolism.
We studied the association of common single nucleotide polymorphisms (SNPs) in the ABCAl gene with HDL-C levels and coronary risk in a cohort of subjects with T2D. We Studied 5 SNPs: +69C>T. +378G>C, R219K, 1883M, and R1587K.
The C allele of +378G>C was significantly associated with lower HDL-C concentrations (P =.04); and the M allele of 1883M, 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 K 1587 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 ABCAl had a moderate influence on HDL-C levels and/or coronary heart disease in patients with T2D. These 2 effects were independent.