A major locus influencing plasma high-density lipoprotein cholesterol levels in the San Antonio Family Heart Study. Segregation and linkage analyses.
A major locus influencing plasma high-density lipoprotein cholesterol levels in the San Antonio Family Heart Study. Segregation and linkage analyses.
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圣安东尼奥家庭心脏研究中影响血浆高密度脂蛋白胆固醇水平的主要基因座。
DOI：
10.1161/01.atv.15.10.1730
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Hixson,JE
中科院分区：
文献类型：
--
作者：
Mahaney,MC;Blangero,J;Rainwater,DL;Comuzzie,AG;VandeBerg,JL;Stern,MP;MacCluer,JW;Hixson,JE
为了检测和测量单个基因座对 HDL 胆固醇 (HDL-C) 血浆浓度定量变化的影响，我们对 25 个随机确定的谱系中 526 名墨西哥裔美国人的数据进行了统计遗传分析。通过使用最大似然复合分离分析，我们发现了具有共显性混合模型的主要位点的证据，其中包括表型平均值、标准差、低 HDL-C 等位基因的相对频率和血浆 HDL-C 水平的遗传力，以及性别（基因型特异性）、年龄与性别、年龄 2 与性别、载脂蛋白 (apo)AI 和甘油三酯（基因型）血浆浓度的影响具体）、外源性激素的使用以及不受限制的一般模型下的绝经状态。四个协变量的纳入（除了性别和年龄对性别的影响）占总血浆 HDL-C 水平方差的近 79%。在其余 21% 的方差中，检测到的主要位点在男性中约占 55%，在女性中约占 21%；基因对变异的总遗传贡献在男性中约为 82%，在女性中约为 69%。连锁分析与分离分析中的外显率参数估计排除了检测到的主要基因座和以下候选基因座标记之间的紧密连锁：apoAI/apoCIII 基因组区域 (P<.05)、apoB (P<.01)、肝脂肪酶 (P<.001)、脂蛋白脂肪酶 (P<.001) 和 LDL 受体 (P<.001)。虽然不排除 apoE 位点 (LOD=-0.348,P<.21)，但分析并未支持它与检测到的主要位点之间的紧密联系。
To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P<.05), apoB (P<.01), hepatic lipase (P<.001), lipoprotein lipase (P<.001), and the LDL receptor (P<.001). While not excluding the apoE locus (LOD=−0.348,P<.21), the analysis provided no support for tight linkage between it and the detected major locus.