APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease

Lee, Kenny W.J; Ayyobi, Amir F; Frohlich, Jiri J; Hill, John S

doi:10.1016/j.atherosclerosis.2004.04.024

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Volume 176, Issue 1 , Pages 165-172, September 2004

APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FER_HDL but is not a risk factor for coronary artery disease

Kenny W.J Lee
- James Hogg iCAPTURE Centre of Cardiovascular and Pulmonary Research and the Healthy Heart Program, St. Paul’s Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
Amir F Ayyobi
- Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA
Jiri J Frohlich
- James Hogg iCAPTURE Centre of Cardiovascular and Pulmonary Research and the Healthy Heart Program, St. Paul’s Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
John S Hill
- James Hogg iCAPTURE Centre of Cardiovascular and Pulmonary Research and the Healthy Heart Program, St. Paul’s Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
- Corresponding author. Tel.: +1-604-806-8616; fax: +1-604-806-8590.

Received 1 December 2003; received in revised form 30 March 2004; accepted 4 April 2004.

Abstract

Variation in the APOA5 gene has been shown to be associated with triglyceride levels in several independent population studies. It was our objective to determine if a relationship existed between selected genotypes or haplotypes of the APOA5 gene and findings on selective coronary angiography (SCA) in an independent cohort. The Vancouver SCA Cohort consists of individuals referred for angiography between 1993 and 1995. DNA was extracted from 537 patients and analyzed for the −1131T>C and the c.56C>G polymorphisms which define three common haplotypes of the APOA5 gene. Plasma triglycerides and the fractional esterification rate in apoB-depleted lipoproteins (FER_HDL), an index of high-density lipoprotein (HDL) composition, were significantly higher (P = 0.01 and P = 0.001, respectively), and HDL cholesterol (HDL-C) was significantly lower (P = 0.03) in Caucasians with genotypes containing the minor allele of the −1131T>C polymorphism compared to the homozygotes for the major allele. However, there was no relationship between the c.56C>G polymorphism of the APOA5 gene and any of the measured lipid and lipoprotein parameters. Subjects homozygous for the common haplotype APOA5*1 had decreased triglyceride levels and FER_HDL (P = 0.04 and P < 0.001, respectively) and increased HDL-C levels (P = 0.01) compared to subjects with all other haplogenotypes. Multivariate linear regression analysis indicated that the −1131T>C polymorphism remained an independent predictor of triglyceride, HDL-C, and FER_HDL following adjustment of several variables including age, gender, body mass index, diabetes, lipid lowering and β-blocker medication. The APOA5*1/*1 haplogenotype remained an independent predictor of HDL-C and FER_HDL following adjustment of the same variables. The relationship between APOA5 genotype or haplogenotype and FER_HDL remained significant even after the addition of both HDL-C and triglyceride to the model. However, there was no association between APOA5 gene polymorphisms or haplotypes and coronary artery disease as determined by angiography.