Associations between two common polymorphisms in the ABCA1 gene and subclinical atherosclerosis: Multi-Ethnic Study of Atherosclerosis (MESA)

Objective: ABCA1 controls the first step in reverse cholesterol transport. The potential associations between G1051A (R219K) and -565C/T genetic polymorphisms in the ABCA1 gene, high-density lipoprotein cholesterol (HDL-C) and subclinical cardiovascular disease in the general population remains unclear. We examined these associations in a sample of Multi-Ethnic Study of Atherosclerosis (MESA) participants. Methods: Nine hundred and sixty-nine MESA participants were genotyped and underwent CT examinations for coronary artery calcification (CAC) and carotid ultrasound examinations for intima media thickness. Genetic association analyses were performed. Results: The AA genotype was associated with a 2.4 mg/dl higher HDL-C, adjusting for age, gender, race/ethnicity and clinic site (p = 0.04). There was a 28% lower prevalence of CAC (p = 0.002) in those with AA genotype that persisted after further adjustment for HDL-C. There were no significant associations between -565 C/T genotype and HDL-C. There were trends towards a higher prevalence of CAC in those with CT (PR = 1.13, p = 0.08) and TT (PR = 1.16, p = 0.08) genotypes, compared with CC genotype. Neither G1051A nor -565C/T polymorphisms were associated with carotid intima media thickness. Conclusion: The AA genotype of the G1051A polymorphism is associated with slightly higher HDL-C and lower prevalence of CAC and thus may protect against subclinical cardiovascular disease. The T allele of -565 C/T polymorphism may increase risk for subclinical cardiovascular disease.