title: ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore.
abstract: Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.
authors.affiliation: Department of Pediatrics, National University of Singapore, 5 Lower Kent Ridge Road, 119074, Singapore.
authors.forename: Jenny Hui-Hui
authors.initials: JH
authors.lastname: Tan
authors.forename: Poh-Sim
authors.initials: PS
authors.lastname: Low
authors.forename: Yong-Seng
authors.initials: YS
authors.lastname: Tan
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Tong
authors.forename: Nilmani
authors.initials: N
authors.lastname: Saha
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Chew-Kiat
authors.initials: CK
authors.lastname: Heng
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000409:Alanine / Q000235:genetics; D016632:Apolipoprotein A-I / Q000097:blood; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007194:India / Q000208:ethnology; D007532:Isoleucine / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008715:Methionine / Q000235:genetics; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D012846:Singapore; D013912:Threonine / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D014633:Valine / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D007532:Isoleucine; D013912:Threonine; D008715:Methionine; D014633:Valine; D003545:Cysteine; D000409:Alanine; D005998:Glycine