Quantitative Transmission Disequilibrium Test를 이용한 지질대사관련 유전자의 혈중 지질농도 결정에 미치는 영향분석

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(TM) 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.