载脂蛋白 A1/C3/A5 单倍型与血脂水平。

Apolipoprotein A1/C3/A5 haplotypes and serum lipid levels.

机构信息

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, People's Republic of China.

出版信息

Lipids Health Dis. 2011 Aug 19;10:140. doi: 10.1186/1476-511X-10-140.

DOI:10.1186/1476-511X-10-140

PMID:21854571

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3170230/

Abstract

BACKGROUND

The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels in the general Chinese population.

METHODS

A total of 1030 unrelated subjects (492 males and 538 females) aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoA1 -75 bp G>A, ApoC3 3238C>G, ApoA5 -1131T>C, ApoA5 c.553G>T and ApoA5 c.457G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Pair-wise linkage disequilibria and haplotype analysis among the five SNPs were estimated.

RESULTS

The levels of high-density lipoprotein cholesterol (HDL-C) and ApoA1 were lower in males than in femailes (P < 0.05 for each). The allelic and genotypic frequencies of the SNPs were no significant difference between males and females except ApoC3 3238C>G. There were 11 haplotypes with a frequency >1% identified in the cluster in our population. At the global level, the haplotypes comprised of all five SNPs were significantly associated with all seven lipid traits. In particular, haplotype G-G-C-C-A (6%; in the order of ApoA5 c.553G>T, ApoA5 c.457G>A, ApoA5 -1131T>C, ApoC3 3238C>G, and ApoA1 -75bp G>A) and G-A-T-C-G (4%) showed consistent association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and the ApoA1/ApoB ratio. In addition, carriers of haplotype G-G-T-C-G (26%) had increased serum concentration of HDL-C and ApoA1, whereas carriers of G-G-C-G-G (15%) had high concentrations of TC, triglyceride (TG) and ApoB. We also found that haplotypes with five SNPs explain much more serum lipid variation than any single SNP alone, especially for TG (4.4% for haplotype vs. 2.4% for -1131T>C max based on R-square) and HDL-C (5.1% for haplotype vs. 0.9% for c.553G>T based on R-square). Serum lipid parameters were also correlated with genotypes and several environment factors.

CONCLUSIONS

Several common SNPs and their haplotypes in the ApoA1/C3/A5 gene cluster are closely associated with modifications of serum lipid parameters in the general Chinese population.

摘要

背景

载脂蛋白（Apo）A1/C3/A4/A5 基因簇中单核苷酸多态性（SNPs）与血清脂质谱的关联并不一致。本研究旨在检测中国人群中 ApoA1/C3/A5 基因多态性及其单倍型与血清脂质水平之间的关联。

方法

从我们之前的分层随机聚类样本中随机选择了 1030 名无血缘关系的受试者（492 名男性和 538 名女性），年龄为 15-89 岁。通过聚合酶链反应和限制性片段长度多态性结合凝胶电泳检测 ApoA1-75bp G>A、ApoC3 3238C>G、ApoA5-1131T>C、ApoA5 c.553G>T 和 ApoA5 c.457G>A 的基因分型，然后通过直接测序进行验证。估计了五个 SNP 之间的连锁不平衡和单倍型分析。

结果

男性的高密度脂蛋白胆固醇（HDL-C）和 ApoA1 水平低于女性（P<0.05）。除了 ApoC3 3238C>G 之外，男性和女性之间 SNP 的等位基因和基因型频率没有显著差异。在我们的人群中，在聚类中发现了 11 个频率>1%的单倍型。在全球水平上，包含所有五个 SNPs 的单倍型与所有七种脂质特征显著相关。特别是，单倍型 G-G-C-C-A（6%；按 ApoA5 c.553G>T、ApoA5 c.457G>A、ApoA5-1131T>C、ApoC3 3238C>G 和 ApoA1-75bp G>A 的顺序排列）和 G-A-T-C-G（4%）与总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、ApoA1、ApoB 和 ApoA1/ApoB 比值一致相关。此外，携带单倍型 G-G-T-C-G（26%）的个体血清 HDL-C 和 ApoA1 浓度升高，而携带 G-G-C-G-G（15%）的个体 TC、甘油三酯（TG）和 ApoB 浓度升高。我们还发现，包含五个 SNP 的单倍型比任何单个 SNP 单独解释了更多的血清脂质变化，尤其是对于 TG（单倍型为 4.4%，基于 R-square 的-1131T>C max 为 2.4%）和 HDL-C（单倍型为 5.1%，基于 R-square 的 c.553G>T 为 0.9%）。血清脂质参数与基因型和几种环境因素也相关。