ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore

• Published in: Human genetics Vol. 113; no. 2; pp. 106 - 117
• Main Authors: TAN, Jenny Hui-Hui, LOW, Poh-Sim, TAN, Yong-Seng, TONG, Ming-Chuan, NILMANI SAHA, HONGYUAN YANG, HENG, Chew-Kiat
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-07-2003; Berlin Springer Nature B.V; New York, NY
• Subjects: ABCA1 gene; Alanine - genetics; Apolipoprotein A-I - blood; Apolipoproteins; Asian Continental Ancestry Group - genetics; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Blood lipids; Case-Control Studies; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; coronary artery disease; Coronary Disease - blood; Coronary Disease - ethnology; Coronary Disease - genetics; Coronary heart disease; Cysteine - genetics; European Continental Ancestry Group - genetics; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Genotype; Glycine - genetics; Haplotypes; Humans; India - ethnology; Isoleucine - genetics; Linkage Disequilibrium - genetics; Lipids - blood; Lipoprotein A; Low density lipoproteins; Malaysia - ethnology; Male; Methionine - genetics; Molecular and cellular biology; Polymorphism, Genetic; Sequence Analysis, DNA; Singapore; Single nucleotide polymorphisms; Threonine - genetics; Triglycerides - blood; Valine - genetics; Singapore; Genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-003-0943-3

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.