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

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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.

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Acknowledgements

This study was supported by grant NMRC/0408/2000 from the National Medical Research Council.

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Authors and Affiliations

  1. Department of Pediatrics, National University of Singapore, 5 Lower Kent Ridge Road, 119074, Singapore

    Jenny Hui-Hui Tan, Poh-Sim Low, Nilmani Saha & Chew-Kiat Heng

  2. Department of Biochemistry, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore

    Hongyuan Yang

  3. National Heart Center, 17 Third Hospital Avenue, 168752, Singapore

    Yong-Seng Tan & Ming-Chuan Tong

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  1. Jenny Hui-Hui Tan
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  2. Poh-Sim Low
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  3. Yong-Seng Tan
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  7. Chew-Kiat Heng
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Correspondence to Chew-Kiat Heng.

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H. Yang and C.-K. Heng contributed equally to this work

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Tan, J.HH., Low, PS., Tan, YS. et al. ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore. Hum Genet 113, 106–117 (2003). https://doi.org/10.1007/s00439-003-0943-3

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  • DOI: https://doi.org/10.1007/s00439-003-0943-3

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