Cai Guowen, Cole Shelley A, Butte Nancy, Bacino Carlos, Diego Vincent, Tan Karen, Göring Harald H, O'Rahilly Stephen, Farooqi I Sadaf, Comuzzie Anthony G
U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Obesity (Silver Spring). 2006 Sep;14(9):1596-604. doi: 10.1038/oby.2006.184.
Genetic components of energy homeostasis contributing to childhood obesity are poorly understood. Genome scans were performed to identify chromosomal regions contributing to physical activity and dietary intake traits in Hispanic children participating in the VIVA LA FAMILIA Study.
We report linkage findings on chromosome 18 for physical activity and dietary intake in 1030 siblings from 319 Hispanic families. Measurements entailed physical activity by accelerometry, dietary intake by two 24-hour recalls, and genetic linkage analyses using SOLAR software.
Significant heritabilities were seen for physical activity and dietary intake, ranging from 0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in sedentary activity mapped to markers D18S1102-D18S64 on chromosome 18 [logarithm of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R) resides. Quantitative trait loci (QTLs) for total activity counts, percentage time in light or in moderate activity, and carbohydrate intake and percentage of energy intake from carbohydrates were detected in the same region (LOD = 2.28, 2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in MC4R (G55V) was detected in six obese relatives, but not in the rest of the cohort. Removal of these MC4R-deficient subjects from the analysis reduced the LOD score for sedentary activity to 3.94.
Given its role in the regulation of food intake and energy expenditure, MC4R is a strong positional candidate gene for the QTL on chromosome 18 detected for physical activity and dietary intake in Hispanic children.
人们对导致儿童肥胖的能量平衡遗传成分了解甚少。进行基因组扫描以确定参与“活力家庭研究”的西班牙裔儿童中，对身体活动和饮食摄入特征有影响的染色体区域。
我们报告了对来自319个西班牙裔家庭的1030名兄弟姐妹进行身体活动和饮食摄入的18号染色体连锁研究结果。测量方法包括通过加速度计测量身体活动、通过两次24小时饮食回顾记录饮食摄入，并使用SOLAR软件进行基因连锁分析。
除剧烈活动外（h2 = 0.18），身体活动和饮食摄入显示出显著的遗传力，范围从0.46到0.69。久坐活动时间百分比与18号染色体上的标记D18S1102 - D18S64相关[优势对数（LOD）分数 = 4.07]，黑皮质素4受体基因（MC4R）位于该区域。在同一区域检测到总活动计数、轻度或中度活动时间百分比、碳水化合物摄入量以及碳水化合物能量摄入量百分比的数量性状位点（QTL）（LOD分别为2.28、2.79、2.2、1.84和1.51）。在6名肥胖亲属中检测到MC4R的一种新的功能丧失突变（G55V），但在其余队列中未检测到。从分析中去除这些MC4R缺陷受试者后，久坐活动的LOD分数降至3.94。
鉴于MC4R在食物摄入和能量消耗调节中的作用，它是在西班牙裔儿童中检测到的18号染色体上身体活动和饮食摄入QTL的有力位置候选基因。
