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 2.4mg/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.


CONCLUSIONS
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.
Benton
Jeana L
JL
The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ding
Jingzhong
J
Tsai
Michael Y
MY
Shea
Steven
S
Rotter
Jerome I
JI
Burke
Gregory L
GL
Post
Wendy
W
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011859:Radiography; D014463:Ultrasonography
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL