1 Department of Cardiology, Marmara University School of Medicine , Istanbul, Turkey .
OMICS. 2013 Dec;17(12):636-45. doi: 10.1089/omi.2013.0066. Epub 2013 Aug 29.
Cardiovascular risk factors and atherosclerosis precursors were examined in 365 Turkish children and adolescents. Study participants were recruited at five different state schools. We tested single and multi-locus effects of six polymorphisms from five candidate genes, chosen based on prior known association with lipid levels in adults, for association with low (≤10th percentile) high density lipoprotein cholesterol (HDL-C) and high (≥90th percentile) triglycerides (TG), and the related continuous outcomes. We observed an association between CETP variant rs708272 and low HDL-C (allelic p=0.020, genotypic p=0.046), which was supported by an independent analysis, PRAT (PRAT control p=0.027). Sex-stratified logistic regression analysis showed that the B2 allele of rs708272 decreased odds of being in the lower tenth percentile of HDL-C measurements (OR=0.36, p=0.02) in girls; this direction of effect was also seen in boys but was not significant (OR=0.64, p=0.21). Logistic regression analysis also revealed that the T allele of rs6257 (SHBG) decreased odds of being in the top tenth percentile of TG measurements in boys (OR=0.43, p=0.03). Analysis of lipid levels as a continuous trait revealed a significant association between rs708272 (CETP) and LDL-C levels in males (p=0.02) with the B2B2 genotype group having the lowest mean LDL-C; the same direction of effect was also seen in females (p=0.05). An effect was also seen between rs708272 and HDL-C levels in girls (p=0.01), with the B2B2 genotype having the highest mean HDL-C levels. Multi-locus analysis, using quantitative multifactor dimensionality reduction (qMDR) identified the previously mentioned CETP variant as the best single locus model, and overall model, for predicting HDL-C levels in children. This study provides evidence for association between CETP and low HDL-C phenotype in children, but the results appear to be weaker in children than previous results in adults and may also be subject to gender effects.
我们在 365 名土耳其儿童和青少年中检查了心血管危险因素和动脉粥样硬化前体。研究参与者是在五所不同的国立学校招募的。我们测试了六个候选基因中六个多态性的单基因和多基因效应，这些基因是基于先前与成年人血脂水平相关的关联选择的，与低（≤第 10 个百分位数）高密度脂蛋白胆固醇（HDL-C）和高（≥第 90 个百分位数）甘油三酯（TG）相关，以及相关的连续结果。我们观察到 CETP 变异 rs708272 与低 HDL-C 之间存在关联（等位基因 p=0.020，基因型 p=0.046），这一结果得到了 PRAT（PRAT 对照 p=0.027）的独立分析的支持。性别分层逻辑回归分析显示，rs708272 的 B2 等位基因降低了女孩处于 HDL-C 测量第 10 个百分位数以下的可能性（OR=0.36，p=0.02）；这种效应在男孩中也有出现，但不显著（OR=0.64，p=0.21）。逻辑回归分析还表明，rs6257（SHBG）的 T 等位基因降低了男孩处于 TG 测量第 10 个百分位数以上的可能性（OR=0.43，p=0.03）。作为连续特征的脂质水平分析显示，rs708272（CETP）与男性 LDL-C 水平之间存在显著关联（p=0.02），B2B2 基因型组的 LDL-C 水平最低；在女性中也观察到相同的效应（p=0.05）。rs708272 与女孩的 HDL-C 水平之间也存在关联（p=0.01），B2B2 基因型组的 HDL-C 水平最高。使用定量多因素维度缩减（qMDR）的多基因分析确定了先前提到的 CETP 变异体是预测儿童 HDL-C 水平的最佳单基因模型和整体模型。这项研究为儿童 CETP 与低 HDL-C 表型之间的关联提供了证据，但与成年人以前的结果相比，结果在儿童中似乎较弱，并且可能也受到性别效应的影响。
