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

Benton, Jeana L.; Ding, Jingzhong; Tsai, Michael Y.; Shea, Steven; Rotter, Jerome I.; Burke, Gregory L.; Post, Wendy

doi:10.1016/j.atherosclerosis.2006.06.024

« Previous Next »Atherosclerosis
Volume 193, Issue 2 , Pages 352-360, August 2007

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

Jeana L. Benton
- The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Jingzhong Ding
- Department of Internal Medicine/Geriatrics, Wake Forest University, Winston-Salem, NC, United States
Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, United States
Steven Shea
- Department of Medicine, Columbia University, New York, NY, United States
- Department of Epidemiology, Columbia University, New York, NY, United States
Jerome I. Rotter
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
Gregory L. Burke
- Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC, United States
Wendy Post
- Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Blalock 910H, 600 N. Wolfe Street, Baltimore, MD 21287, United States
- Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
- Corresponding author. Tel.: +1 410 955 7376; fax: +1 443 287 0121.

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.

Keywords: ABCA1, HDL cholesterol, Coronary calcium, Candidate genes, Genetic polymorphisms, Atherosclerosis