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

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

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 2.4 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.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
JournalAtherosclerosis
Volume193
Issue number2
DOIs
StatePublished - Aug 2007

Bibliographical note

Funding Information:
This research was supported by contracts N01-HC-95159 through N01-HC-95169 (MESA) and RO1 HL071205 (MESA Family) from the National Heart, Lung, and Blood Institute and the Hopkins GCRC grant M01-RR000052 from the National Center for Research Resources, National Institutes of Health. Dr. Post is supported by the Paul Beeson Physician Faculty Scholars in Aging Program and the Johns Hopkins Donald W. Reynolds Cardiovascular Research Center. The authors thank the other investigators, the staff, and the participants of MESA for their valuable contributions.

Keywords

  • ABCA1
  • Atherosclerosis
  • Candidate genes
  • Coronary calcium
  • Genetic polymorphisms
  • HDL cholesterol

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