Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25
Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25
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DOI：
10.2337/diabetes.53.10.2676
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发表时间：
2004-10-01
期刊：
影响因子：
7.7
通讯作者：
Chan, JCN
中科院分区：
文献类型：
--
作者：
Ng, MCY;So, WY;Chan, JCN
我们在香港家族性糖尿病研究中进行了常染色体基因组扫描，以定位代谢综合征(MES)和相关性状的基因座。我们选择了55个家系，137个受影响的成员(121个受影响的亲属对)进行MES的非参数连锁分析。我们还选择了179个家庭，897个成员(2,127个相对对)，对7个与MES相关的性状进行了基于方差成分的连锁分析：腰围、收缩和舒张压(BP)、甘油三酯、高密度脂蛋白、空腹血糖和胰岛素抵抗指数(稳态模型评估的胰岛素抵抗指数[HOMA%IR])。分析发现，有三个区域显示了MES的连锁，并显示了代谢性状的重叠信号：第1号染色体位于169.5-181.5 cM(MES的对数=4.5，腰围=3.71，舒张压=1.24)，2号染色体位于44.1-57.3 cM(LOD=2.22，空腹血糖=2.07，舒张压=1.29)，16号染色体位于45.2-65.4 cM(LOD=1.75，HOMA%IR)，和1.25的高密度脂蛋白胆固醇)。其他显示关联的区域包括舒张压的染色体5q；甘油三酯的2q、3q、6q、9q、10q和17q；高密度脂蛋白胆固醇的12p、12q和22q；以及HOMA%IR的6q。模拟研究表明，1号染色体区域在全基因组范围内与MES和腰围显著相关(P全基因组范围分别为0.002和0.019)。综上所述，我们在染色体1q21-q25上发现了一个易感基因，该易感基因与多种代谢异常，尤其是肥胖的发病有关。我们的结果证实了先前关于糖尿病和相关表型的研究结果。我们还提出了可能有助于香港中国人MES发生的其他基因座的位置。
We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relative pairs) for variance component-based linkage analyses on seven MES-related traits: waist circumference, systolic and diastolic blood pressure (BP), triglyceride, HDL cholesterol, fasting plasma glucose, and insulin resistance index (insulin resistance index by homeostasis model assessment [HOMA%IR]). Analyses revealed three regions that showed suggestive linkage for MES and also showed overlapping signals for metabolic traits: chromosome 1 at 169.5-181.5 cM (logarithm of odds [LOD] = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic BP), chromosome 2 at 44.1-57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma glucose, and 1.29 for diastolic BP), and chromosome 16 at 45.2-65.4 cM (LOD = 1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that showed suggestive linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q, 9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C; and 6q for HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the chromosome 1 region to both MES and waist circumference (Pgenome-wide = 0.002 and 0.019, respectively). In summary, we have found a susceptibility locus on chromosome 1q21-q25 involved in the pathogenesis of multiple metabolic abnormalities, in particular obesity. Our results confirm the findings of previous studies on diabetes and related phenotypes. We also suggest the locations of other loci that may contribute to the development of MES in Hong Kong Chinese.