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Park, Eom, Jang, and Park: Estimating the Genetic Variance of Five Lipid-Relevant Genes for Determining the Plasma Lipid Profiles
Original Article
Korean Circulation Journal

Korean Circulation Journal 2008; 38(4): 197-204.

Published online: 30 April 2008

DOI: https://doi.org/10.4070/kcj.2008.38.4.197

Estimating the Genetic Variance of Five Lipid-Relevant Genes for Determining the Plasma Lipid Profiles

Chanmi Park, PhD1, Sangmi Eom, MS2, Yangsoo Jang, MD1, Hyun-Young Park, MD2

1Cardiovascular Genome Center, Yonsei University College of Medicine, Seoul, Korea.

2Division of Cardiovascular Diseases, Center for Biomedical Sciences, National Institutes of Health, Seoul, Korea.

Correspondence: Hyun-Young Park, MD, Division of Cardiovascular Diseases, Center for Biomedical Sciences, National Institutes of Health, 194 Tongil-no, Eunpyeong-gu, Seoul 122-701, Korea. Tel: 82-2-380-1534, Fax: 82-2-388-0924, hypark65@nih.go.kr

Received 18 October 2007       Revised 16 November 2007       Accepted 26 November 2007

Copyright © 2008 The Korean Society of Cardiology

Abstract

Background and Objectives

The plasma lipid levels play crucial roles in the development of atherosclerotic diseases. We estimated the genetic variance of the lipid levels according to the contributions of the single nucleotide polymorphisms (SNPs) and haplotypes in 5 candidate genes.

Subjects and Methods

We selected SNPs in the ATP binding cassette A1 (ABCA1) gene, the apolipoprotien A5 (APOA5), apolipoprotien E (APOE) gene, the cholesterol ester transfer protein (CETP) gene and the hepatic triglyceride lipase (LIPC) gene in 383 individuals from 100 Korean families. The genotype was determined by Orchid's SNP-IT™ technology. The association analysis of the quantitative traits was performed using the quantitative transmission disequilibrium test.

Results

A component analysis of the phenotypic variance explained 24.7% of the genetic variance on the total cholesterol, 26.4% of the genetic variance of the high density lipoprotein (HDL)-cholesterol, 11% of the genetic variance of the triglycerides, 35.6% of the genetic variance of the low density lipoprotein (LDL)-cholesterol and 18.9% of the genetic variance of the LDL-C/HDL-C, respectively. The association of the SNPs in the candidate genes explained a major fraction of the genetic phenotypic variance in the LDL-C/HDL-C ratio, but not in the other lipid profiles. The association with SNPs explained 38.5% of the variance for the total cholesterol, 32.2% of the variance for HDL-cholesterol and 29.5% of the variance for LDL-cholesterol relative to the polygenic background. An analysis of the contribution of each gene to the genetic variance showed that ABCA1, APOE, CETP and LIPC influenced the variations in total cholesterol, LDL-cholesterol and LDL-C/HDL-C. The variation in HDL-cholesterol was influenced by ABCA1, APOA5 and APOE.

Conclusion

We identified that the genetic variance for the total cholesterol, HDL-cholesterol and LDL-cholesterol, and the LDL-C/HDL-C ratio was significantly influenced by the genetic polymorphisms in 5 candidate genes in the Korean population. Further studies are necessary to identify other genes that can explain a major fraction of the genetic variance for the lipid levels.

Keywords: Lipids, Single nucleotide polymorphism

Figures and Tables

Table 1
Clinical characteristics of study population
kcj-38-197-i001

Mean±SD. BMI: body mass index, TC: total cholesterol, HDL-C: high density lipoprotein-cholesterol, TG: triglycerides, LDL-C: low density lipoprotein-cholesterol, LDL-C /HDL-C: LDL-cholesterol/HDL-cholesterol ratio

Table 2
SNP characteristics including localization, rare allele frequencies in unrelated founders
kcj-38-197-i002

SNP: single nucleotide polymorphism, ABCA1: ATP binding cassette A1, APOA5: apolipoprotien A5, APOE: apolipoprotien E, CETP: cholesterol ester transfer protein, LIPC: hepatic triglyceride lipase, UTR: untranslated region, syn: synonymous, non-syn: non-synonymous

Table 3
Haplotypes estimated from the study population and haplotype frequencies
kcj-38-197-i003

SNP: single nucleotide polymorphism, ABCA1: ATP binding cassette A1, APOA5: apolipoprotien A5, APOE: apolipoprotien E, CETP: cholesterol ester transfer protein, LIPC: hepatic triglyceride lipase

Table 4
Partition of phenotypic variance into variance components
kcj-38-197-i004

Venv: environmental variance component, Vpoly: polygenic variance component, Vhap: variance component due to haplotype as regressor, VSNP: variance component due to SNP genotype as regressor. In the 'null model' only Venv and Vpoly are estimated. In the 'full model' haplotype or SNP, data are included as fixed effect. Significance of multiple haplotype or SNPs was tested using likelihood ratio test comparing the likelihoods of the 'null model' and 'full model'. TC: total-cholesterol, HDL-C: high density lipoprotein-cholesterol, lnTG: logarithmic value of triglycerides, LDL-C: low density lipoprotein-cholesterol, LDL-C/HDL-C: LDL-cholesterol/HDL-cholesterol ratio, LR test: likelihood ratio test

Table 5
Locuswise contribution and its significance of SNPs to the genetic variance of lipid profiles
kcj-38-197-i005

QTDT procedure was performed to calculate the likelihood of the data under a specified model. The full model contains all variants within all genes as regressors. For the reduced model, variants of the tested gene locus were excluded. SNPs: single nucleotide polymorphisms, ABCA1: ATP binding cassette A1, APOA5: apolipoprotien A5, APOE: apolipoprotien E, CETP: cholesterol ester transfer protein, LIPC: hepatic triglyceride lipase, TC: total-cholesterol, HDL-C: high density lipoprotein-cholesterol, lnTG: logarithmic value of triglycerides, LDL-C: low density lipoprotein-cholesterol, LDL-C/HDL-C: LDL-cholesterol/HDL-cholesterol ratio, LR test: likelihood ratio test

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