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Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans

Austin, MA; Talmud, PJ; Farin, FM; Nickerson, DA; Edwards, KL; Leonetti, D; ... Fujimoto, WY; + view all (2004) Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans. BBA-MOL BASIS DIS , 1688 (1) 1 - 9. 10.1016/j.bbadis.2003.10.003.

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Abstract

A new apolipoprotein (apo) gene, APOA5, was recently identified on chromosome 11q23, and common variants in the gene have been associated with plasma triglyceride (TG) levels in several studies. The purpose of the present study was to examine the association of five single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene with low-density lipoprotein (LDL) particle size using a community-based sample of Japanese American families, including examining whether the associations with LDL size are independent of, or primarily reflecting, TG levels. Genetic association analyses were performed using 154 unrelated individuals, quantitative transmission disequilibrium tests (TDT) in 238 nuclear families, a sample of 24 hypertriglyceridemic subjects with matched, normotriglyceridemic controls, and using haplotype analyses. There was a high degree of allelic association between several of the SNPs, with complete linkage disequilibrium, (LD) between - 1131C>T and the - 3A>G SNP which alters a potential Kozak sequence. All approaches demonstrated associations between the - 3A>G APOA5 variant and both decreased LDL size and increased TG levels. The frequency of the rare allele was higher than reported for Caucasian, Hispanic, and African Americans, but similar to that in Japan and China. Therefore, the haplotype containing the - 1131C and - 3G variants, and possibly specifically the - 3A>G SNP in APOA5, may be a major genetic determinant of LDL particle size and TG levels among ethnic Asians. (C) 2003 Elsevier B.V. All rights reserved.

Type:Article
Title:Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans
DOI:10.1016/j.bbadis.2003.10.003
Keywords:apolipoprotein, cardiovascular disease, genetics, low-density lipoprotein, triglyceride, LOW-DENSITY-LIPOPROTEIN, CORONARY-HEART-DISEASE, FAMILIAL COMBINED HYPERLIPIDEMIA, DEPENDENT DIABETES-MELLITUS, INHERITED SUSCEPTIBILITY, ENHANCED SUSCEPTIBILITY, LINKAGE DISEQUILIBRIUM, MYOCARDIAL-INFARCTION, PLASMA TRIGLYCERIDES, COMMON POLYMORPHISM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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