Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)
Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)
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DOI：
10.1016/j.atherosclerosis.2006.02.006
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发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Borecki, Ingrid B.
中科院分区：
文献类型：
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作者：
Feitosa, Mary F.;Province, Michael A.;Borecki, Ingrid B.
进行全基因组连锁扫描，以确定可能具有影响高密度脂蛋白（HDL）胆固醇的数量性状基因座（QTL）的区域。我们发现了 QTL（lod 评分 (LOD) = 1.75，p = 0.00224，q = 0.07649）的暗示性证据，该 QTL 影响 NHLB1 FHS 数据中染色体 15q21 标记 D15S659 上年龄和性别调整的 HDL 胆固醇血浆水平的变化。由于与糖尿病相关的血脂谱的扰动，重复了分析，从样本中排除了糖尿病受试者。尽管样本量减少，但在同一 15 号染色体位置，lod 得分从 1.75 增加到 2.71（p = 0.00021，q = 0.05392）。这一发现表明，在分析中纳入糖尿病受试者可能会混淆 15q21 上 HDL-胆固醇 QTL 的存在。由于代谢变量和生活习惯等重要协变量的已知影响可能与假定的 QTL 相互作用，我们还通过渐进调整分析了 HDL-胆固醇。当将体重指数、吸烟和习惯性饮酒添加到年龄和性别调整中时，我们在完整样本（LOD = 4.77，p = 0.00000 13，q = 0.00016）以及非糖尿病子样本（LOD = 4.52，p = 0.0000025，q = 0.00026）中发现了存在联系的有力证据。位于染色体 15q21 上（D15S659 和 D15S195 标记之间）。这些结果表明，影响 HDL 胆固醇水平的遗传和环境影响有多种途径和因素，通过考虑其中一些已知因素，我们获得了 QTL 影响 HDL 胆固醇水平的有力证据。虽然这种推定的 QTL 也可能对糖尿病有影响，但我们的数据表明，在非糖尿病患者中作用更明显。 15q21 连锁区内的一个重要候选基因是肝脂肪酶 (HL)，它在脂蛋白代谢中起重要作用。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLB1 FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.00000 13, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers).These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.