The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study.
Low HDL-cholesterol (HDL-C) is associated with an increased risk for atherosclerosis, and concentrations are modulated by genetic factors and environmental factors such as smoking. Our objective was to assess whether the association of common single-nucleotide polymorphisms (SNPs) at ABCG5/G8 (i18429G>A, i7892T>C, Gln604GluC>G, 5U145A>C, Tyr54CysA>G, Asp19HisG>C, i14222A>G, and Thr400LysC>A) genes with HDL-C differs according to smoking habit. ABCG5/G8 SNPs were genotyped in 845 participants (243 men and 602 women). ABCG5/G8 (i7892T>C, 5U145A>C, Tyr54CysA>G, Thr400LysC>A) SNPs were significantly associated with HDL-C concentrations (P < 0.001-0.013) by which carriers of the minor alleles at the aforementioned polymorphisms and homozygotes for the Thr400 allele displayed lower HDL-C. A significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5/G8 (Gln604GluC>G, Asp19HisG>C, i14222A>G) SNPs displayed lower concentrations of HDL-C only if they were smokers (P = 0.001-0.025). Also, for ABCG8_Thr400LysC>A SNP, smokers, but not nonsmokers, homozygous for the Thr400 allele displayed lower HDL-C (P = 0.004). Further analyses supported a significant haplotype global effect on lowering HDL-C (P = 0.002) among smokers. In conclusion, ABCG5/G8 genetic variants modulate HDL-C concentrations, leading to an HDL-C-lowering effect and thereby a potential increased risk for atherosclerosis only in smokers.
Junyent
Mireia
M
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Tucker
Katherine L
KL
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Smith
Caren E
CE
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Garcia-Rios
Antonio
A
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Mattei
Josiemer
J
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Lai
Chao-Qiang
CQ
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Parnell
Laurence D
LD
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
Ordovas
Jose M
JM
The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA. Electronic address: jose.ordovas@tufts.edu.
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D019943:Amino Acid Substitution; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics; D001900:Boston; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood* / Q000235:genetics*
C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D008074:Lipoproteins