Associations between two common polymorphisms in the ABCA1 gene and subclinical atherosclerosis: Multi-Ethnic Study of Atherosclerosis (MESA)
Received 15 February 2006; received in revised form 9 May 2006; accepted 9 June 2006. published online 02 August 2006.
Abstract
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 2.4mg/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 −565C/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.
aDivision of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Blalock 910H, 600 N. Wolfe Street, Baltimore, MD 21287, United States
bThe Johns Hopkins University School of Medicine, Baltimore, MD, United States
cDepartment of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
dDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, United States
eDepartment of Medicine, Columbia University, New York, NY, United States
fDepartment of Epidemiology, Columbia University, New York, NY, United States
gMedical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
hDepartment of Public Health Sciences, Wake Forest University, Winston-Salem, NC, United States
iDepartment of Internal Medicine/Geriatrics, Wake Forest University, Winston-Salem, NC, United States
ABSTRACT