title: The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study.
abstract: 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.
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Mireia
authors.initials: M
authors.lastname: Junyent
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Rios
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Josiemer
authors.initials: J
authors.lastname: Mattei
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.affiliation: 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.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: 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*
chemical_list: 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