Common genetic variation in the ATP-binding cassette transporter A1, plasma lipids, and risk of coronary heart disease.
The ATP-binding cassette transporter A-1 (ABCA1) regulates cholesterol efflux from cells and is involved in high-density lipoprotein (HDL) metabolism and atherogenesis. We investigated whether common ABCA1 variants, previously reported to have phenotypic effects in humans, were associated with plasma lipids and CHD in a prospective study of coronary heart disease (CHD) in healthy women. Three polymorphisms in the promoter region (-565C/T, -191G/C, and -17C/G) and two in the coding region (I883M and R1587K) were genotyped in the Nurses' Health Study. During 8 years of follow-up, 249 incident cases of CHD were identified and matched to controls (1:2) on age and smoking. The I883M variant was associated with higher HDL-cholesterol levels among younger women. Nearly complete linkage disequilibrium was observed between -565C/T and -191G/C and their less common alleles predicted a lower risk of CHD (odds ratio of CHD per -191C allele: 0.8; 95% CI, 0.6-1.0). Neither the -17C/G SNP nor the 2 the coding polymorphisms were associated with risk of CHD. The -565C/T and the -191G/C variants were inversely associated with risk of CHD among healthy women, without pronounced effects on plasma lipids.
Jensen
Majken K
MK
Department of Nutrition, Harvard School of Public Health, Boston, MA, United States. mkj@dce.au.dk
Pai
Jennifer K
JK
Mukamal
Kenneth J
KJ
Overvad
Kim
K
Rimm
Eric B
EB
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000483:Alleles; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000737:chemistry; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids