Arnett Donna K, Miller Michael B, Coon Hilary, Ellison R Curtis, North Kari E, Province Michael, Leppert Mark, Eckfeldt John H
Division of Epidemiology, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454, USA.
Hum Genet. 2004 Nov;115(6):468-74. doi: 10.1007/s00439-004-1182-y. Epub 2004 Sep 16.
Recent reports implicate chromosomal regions linked to inter-individual variation in plasma triglycerides. We conducted genome-wide scans to replicate these linkages and/or identify other loci influencing plasma triglycerides in the NHLBI Family Heart Study (FHS). Data were obtained for 501 three-generational families. Genotyping was done by the Utah Molecular Genetics Laboratory and NHLBI Mammalian Genotyping Service; markers from both were placed on one genetic map. Analysis was done using multipoint variance components linkage. Fasting plasma triglycerides were log-transformed and age-, sex-, and field center-adjusted; suggestive linkage evidence was found on chromosome 8 (LOD=2.80 at 89 cM, marker D8S1141). Further adjustment for waist girth, BMI, diabetes, hypertension, and lipid-lowering drugs suggested linkage regions on chromosomes 6 (LOD=2.29 at 79 cM, marker D6S295) and 15 (LOD=1.85 at 43 cM, marker D15S659). Since HDL is correlated with triglycerides and because it was linked to this region on chromosome 15 in FHS, we created a composite triglyceride-HDL phenotype. The combined phenotype LOD score was 3.0 at the same marker on chromosome 15. Chromosome 15 likely harbors a susceptibility locus with an influence on triglycerides and HDL. Regions on chromosomes 6 and 8 may also contain loci contributing to inter-individual variation in plasma triglycerides.
近期报告表明，染色体区域与血浆甘油三酯的个体间差异有关。我们进行了全基因组扫描，以重复这些连锁关系和/或确定影响美国国立心肺血液研究所（NHLBI）家族心脏研究（FHS）中血浆甘油三酯的其他基因座。获取了501个三代家庭的数据。基因分型由犹他分子遗传学实验室和NHLBI哺乳动物基因分型服务中心完成；来自两者的标记被放置在一张遗传图谱上。使用多点方差成分连锁分析进行分析。空腹血浆甘油三酯进行对数转换，并根据年龄、性别和现场中心进行调整；在8号染色体上发现了提示性连锁证据（在89厘摩处LOD = 2.80，标记为D8S1141）。进一步对腰围、体重指数、糖尿病、高血压和降脂药物进行调整后，提示在6号染色体（在79厘摩处LOD = 2.29，标记为D6S295）和15号染色体（在43厘摩处LOD = 1.85，标记为D15S659）上存在连锁区域。由于高密度脂蛋白（HDL）与甘油三酯相关，并且因为它在FHS中与15号染色体上的这个区域连锁，我们创建了一个复合甘油三酯 - HDL表型。在15号染色体上的相同标记处，组合表型的LOD得分为3.0。15号染色体可能含有一个对甘油三酯和HDL有影响的易感基因座。6号和8号染色体上的区域也可能包含导致血浆甘油三酯个体间差异的基因座。
