Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels
Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels
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DOI：
10.1086/302365
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发表时间：
1999-05-01
影响因子：
9.8
通讯作者：
Peltonen, L
中科院分区：
文献类型：
--
作者：
Pajukanta, P;Terwilliger, JD;Peltonen, L
家族性混合性高脂血症（FCHL）是一种常见的易患早发冠心病（CHD）的血脂异常。该疾病的特征在于血清总胆固醇（TC）、甘油三酯（TG）或两者的水平升高。我们最近定位了FCHL的第一个位点，在染色体1 q21-q23上。在本研究中，进行了全基因组筛选额外的FCHL基因座。在第一阶段，我们在35个仔细特点芬兰FCHL家庭的368个多态性标记基因型。通过使用FCHL性状的显性遗传模式，我们鉴定了具有显示LOD得分（Z）值>1.0的标记的六个染色体区域。此外，出现了另外两个显示Z > 2.0且具有TG性状的区域。在第2阶段，我们对这些感兴趣的区域的26个标记和7个额外的FCHL家族进行了基因分型。在连锁分析中，两个染色体区域显示Z > 2.0：10p11.2，Z = 3.20（θ = 0.00），具有TG性状; 21 q21，Z = 2.24（θ = 0.10），具有apoB性状。此外，在受影响的同胞对分析中，另外两个染色体区域产生Z > 2.0：10q11.2- 10 qter产生Z = 2.59的TC性状和Z = 2.29的FCHL，和2 q31产生Z = 2.25的TG性状。我们的研究结果表明，在芬兰的家庭，一些潜在的影响TG水平和一些潜在的影响TC或载脂蛋白B水平的影响FCHL的其他推定位点。
Familial combined hyperlipidemia (FCHL) is a common dyslipidemia predisposing to premature coronary heart disease (CHD). The disease is characterized by increased levels of serum total cholesterol (TC), triglycerides (TGs), or both. We recently localized the first locus for FCHL, on chromosome 1q21-q23. In the present study, a genomewide screen for additional FCHL loci was performed. In stage 1, we genotyped 368 polymorphic markers in 35 carefully characterized Finnish FCHL families. We identified six chromosomal regions with markers showing LOD score (Z) values >1.0, by using a dominant mode of inheritance for the FCHL trait. In addition, two more regions emerged showing Z > 2.0 with a TG trait. In stage 2, we genotyped 26 more markers and seven additional FCHL families for these interesting regions. Two chromosomal regions revealed Z > 2.0 in the linkage analysis: 10p11.2, Z = 3.20 (theta = .00), with the TG trait; and 21q21, Z = 2.24 (theta = .10), with the apoB trait. Furthermore, two more chromosomal regions produced Z > 2.0 in the affected-sib-pair analysis: 10q11.2-10qter produced Z = 2.59 with the TC trait and Z = 2.29 with FCHL, and 2q31 produced Z = 2.25 with the TG trait. Our results suggest additional putative loci influencing FCHL in Finnish families, some potentially affecting TG levels and some potentially affecting TC or apoB levels.