香港华人代谢综合征及相关数量性状的全基因组扫描与1q21 - q25染色体上一个易感位点的确认
Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.
作者信息
Ng Maggie C Y, So Wing-Yee, Lam Vincent K L, Cockram Clive S, Bell Graeme I, Cox Nancy J, Chan Juliana C N
机构信息
Departmetn of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, SAR.
出版信息
Diabetes. 2004 Oct;53(10):2676-83. doi: 10.2337/diabetes.53.10.2676.
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 (P(genome-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.
在香港家族糖尿病研究中,我们进行了常染色体基因组扫描,以绘制代谢综合征(MES)及相关性状的基因座图谱。我们选取了55个家庭中的137名患病成员(121对患病亲属对)进行MES的非参数连锁分析。我们还选取了179个家庭中的897名成员(2127对亲属对),对七个与MES相关的性状进行基于方差成分的连锁分析,这些性状包括腰围、收缩压和舒张压(BP)、甘油三酯、高密度脂蛋白胆固醇、空腹血糖以及胰岛素抵抗指数(通过稳态模型评估得出的胰岛素抵抗指数[HOMA%IR])。分析发现了三个区域,这些区域对MES显示出提示性连锁,并且对代谢性状也显示出重叠信号:1号染色体上169.5 - 181.5 cM处(MES的对数优势[LOD] = 4.50,腰围的LOD = 3.71,舒张压的LOD = 1.24),2号染色体上44.1 - 57.3 cM处(MES的LOD = 2.22,空腹血糖的LOD = 2.07,舒张压的LOD = 1.29),以及16号染色体上45.2 - 65.4 cM处(MES的LOD = 1.75,HOMA%IR的LOD = 1.61,高密度脂蛋白胆固醇的LOD = 1.25)。其他显示提示性连锁的区域包括:5号染色体长臂与舒张压相关;2号染色体长臂、3号染色体长臂、6号染色体长臂、9号染色体长臂、10号染色体长臂和17号染色体长臂与甘油三酯相关;12号染色体短臂、12号染色体长臂和22号染色体长臂与高密度脂蛋白胆固醇相关;6号染色体长臂与HOMA%IR相关。模拟研究表明,1号染色体区域与MES和腰围均存在全基因组显著连锁(全基因组P值分别为0.002和0.019)。总之,我们在1号染色体q21 - q25上发现了一个与多种代谢异常发病机制相关的易感基因座,尤其是肥胖。我们的结果证实了先前关于糖尿病及相关表型研究的发现。我们还指出了其他可能与香港华人MES发病相关的基因座位置。