Melanocortin-4 receptor gene and physical activity in the Quebec Family Study
Melanocortin-4 receptor gene and physical activity in the Quebec Family Study
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DOI：
10.1038/sj.ijo.0802869
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发表时间：
2005-04-01
影响因子：
4.9
通讯作者：
Bouchard, C
中科院分区：
文献类型：
--
作者：
Loos, RJF;Rankinen, T;Bouchard, C
缺乏身体活动是许多慢性疾病的危险因素。低依从性的干预措施，以增加活动表明参与的生物systems.Objective：研究是否序列变异的基因编码的神经肽和受体在弓状核和室旁核的下丘脑有助于在魁北克家庭研究中的身体活动水平的变化。我们对黑皮质素-4受体（MC 4 R）、黑皮质素-3受体（MC 3R）、神经肽-Y（NPY）、神经肽-Y Y1受体（NPY Y1 R）可卡因和安非他明调节转录物（CART）、刺豚鼠相关蛋白（AGRP）和阿黑皮素原（POMC）基因在669名受试者中的表达（年龄（X +/- s.d.）：父母：52 +/- 3.4岁;后代：28 +/- 8.7岁）。总体力活动，中度至剧烈活动，和不活动的表型估计从三天的记录。过去一年的身体活动水平是通过问卷调查评估的。结果：MC 4 R-C-2745 T基因多态性与体力活动表型有显著相关性。T/T基因型中中度至剧烈活动评分最低（P = 0.005），不活动评分最高（P = 0.01）。排除肥胖受试者增加了相关性。对于不活动，MC 4 R-C-2745 T变体的关联在后代中最强（P = 0.002）。T/T后代的不活动评分最高，体重指数最低。CART-A1475 G变异改变了与MC 4 R-C-2745 T的关联;当T/T纯合子也具有A/A CART-A1475 G基因型时，其活性得分最低。没有显着的协会被观察到多态性在其他neuropeptide.CONCLUSION：这些研究结果表明，DNA序列变异MC 4 R基因位点可能有助于久坐的倾向。
Physical inactivity is a risk factor for numerous chronic diseases. Low compliance with interventions to increase activity suggests involvement of biological systems.OBJECTIVE: To examine whether sequence variants in genes encoding neuropeptides and receptors in the arcuate and paraventricular nucleus of the hypothalamus contribute to variations in physical activity level in the Quebec Family Study.METHODS: We genotyped polymorphisms in the melanocortin-4 receptor (MC4R), melanocortin-3 receptor (MC3R), neuropeptide-Y (NPY), neuropeptide-Y Y1 receptor (NPY Y1R), cocaine-and amphetamine-regulated transcript (CART), agouti-related protein (AGRP), and pro-opiomelanocortin (POMC) genes in 669 subjects (age (X +/- s.d.): parents: 52 +/- 3.4 y; offspring: 28 +/- 8.7 y). Total physical activity, moderate-to-strenuous activity, and inactivity phenotypes were estimated from a three-day record. The past year's physical activity level was assessed from a questionnaire. Associations between the physical activity phenotypes and the polymorphisms were analyzed using the MIXED model (SAS).RESULTS: The MC4R-C-2745T variant showed significant associations with physical activity phenotypes. The lowest moderate-to-strenuous activity scores (P = 0.005) and the highest inactivity scores (P = 0.01) emerged in the T/T genotype. Exclusion of obese subjects increased the association. For inactivity, the association of the MC4R-C-2745T variant was strongest in the offspring (P = 0.002). The T/T offspring had both the highest inactivity score and the lowest body mass index. The CART-A1475G variant modified the associations with MC4R-C-2745T; T/T homozygotes had the lowest activity scores when they also had the A/A CART-A1475G genotype. No significant associations were observed with polymorphisms in the other neuropeptides.CONCLUSION: These findings suggest that DNA sequence variation at the MC4R gene locus may contribute to the propensity to be sedentary.