人类载脂蛋白AI基因+83bp处新的MspI多态性：与循环中高密度脂蛋白胆固醇水平升高相关

New MspI polymorphism at +83 bp of the human apolipoprotein AI gene: association with increased circulating high density lipoprotein cholesterol levels.

作者信息

Wang X L, Badenhop R, Humphrey K E, Wilcken D E

机构信息

Department of Cardiovascular Medicine, Prince Henry Hospital, University of New South Wales, Australia.

出版信息

Genet Epidemiol. 1996;13(1):1-10. doi: 10.1002/(SICI)1098-2272(1996)13:1<1::AID-GEPI1>3.0.CO;2-D.

DOI:10.1002/(SICI)1098-2272(1996)13:1<1::AID-GEPI1>3.0.CO;2-D

PMID:8647374

Abstract

We recently showed that loss of a MspI restriction site in the 5'-end (intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or a G to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI gene expression and therefore to plasma high density lipoprotein cholesterol (HDL-C), we explored the association between this MspI polymorphic site and circulating HDL-C levels in 243 healthy Caucasians. There were 143 aged 18-67 years (60 males and 83 females) and 100 aged 6-12 years (58 males and 42 females). We also compared this association with a known MspI polymorphic site, a G to A transition at -75 bp of the apo AI gene. The rare allele (-) frequency for the polymorphism at +83 bp was 4.1% and 22.1% for the polymorphism at -75 bp. Subjects heterozygous for the loss of the MspI restriction site at +83 bp (genotype: M2+-, n = 20) had higher HDL-C levels than M2+2 subjects (mean +/- SD: 1.73 +/- 0.31 vs. 1.41 +/- 0.39 mmol/l, P < 0.05 for adults; 1.71 +/- 0.33 vs. 1.34 +/- 0.29 mmol/l, P < 0.01 for children). Adults with the G to A substitution at -75 bp also had higher HDL-C levels (1.56 +/- 0.36 mmol/l for AA, 1.53 +/- 0.38 mmol/l for GA, and 1.36 +/- 0.38 mmol/l for GG, P < 0.05); this difference was not observed in the children. The MspI polymorphisms at both sites were in linkage disequilibrium. Their joint effect on the HDL-C levels was also significant and individuals with rare alleles (-) at both sites had the highest HDL-C levels. In an analysis of variance, the MspI polymorphism at +83 bp, and at -75 bp and gender independently accounted for 6.5%, 1.7%, and 5.9%, respectively, of the variance in circulating HDL-C levels when age was controlled as a covariate. We conclude that loss of the MspI site by the C to T (+83 bp) and/or the G to A (+84 bp) transitions is highly associated with increased HDL-C levels. The association appears to be more significant than that of the G to A transition at -75 bp.

摘要

我们最近发现，载脂蛋白（apo）AI基因5′端（内含子1）MspI限制性酶切位点的缺失是由C到T的转换（+83 bp）和/或G到A的转换（+84 bp）所致。由于该区域可能与apo AI基因表达的调控相关，进而与血浆高密度脂蛋白胆固醇（HDL-C）有关，我们在243名健康白种人中探究了这个MspI多态性位点与循环HDL-C水平之间的关联。其中143人年龄在18 - 67岁（男性60名，女性83名），100人年龄在6 - 12岁（男性58名，女性42名）。我们还将这种关联与一个已知的MspI多态性位点进行了比较，即apo AI基因-75 bp处的G到A的转换。+83 bp处多态性的罕见等位基因（-）频率为4.1%，-75 bp处多态性的罕见等位基因（-）频率为22.1%。+83 bp处MspI限制性酶切位点缺失的杂合子受试者（基因型：M2+-，n = 20）的HDL-C水平高于M2+2受试者（均值±标准差：成人组为1.73±0.31 vs. 1.41±0.39 mmol/L，P < 0.05；儿童组为1.71±0.33 vs. 1.34±0.29 mmol/L，P < 0.01）。-75 bp处发生G到A替换的成年人HDL-C水平也较高（AA型为1.56±0.36 mmol/L，GA型为1.53±0.38 mmol/L，GG型为1.36±0.38 mmol/L，P < 0.05）；在儿童中未观察到这种差异。两个位点的MspI多态性处于连锁不平衡状态。它们对HDL-C水平的联合效应也很显著，两个位点均具有罕见等位基因（-）的个体HDL-C水平最高。在方差分析中，当将年龄作为协变量进行控制时，+83 bp处的MspI多态性、-75 bp处的MspI多态性和性别分别独立解释了循环HDL-C水平变异的6.5%、1.7%和5.9%。我们得出结论，由C到T（+83 bp）和/或G到A（+84 bp）转换导致的MspI位点缺失与HDL-C水平升高高度相关。这种关联似乎比-75 bp处G到A的转换更为显著。