Nakayama Kazuhiro, Miyashita Hiroshi, Iwamoto Sadahiko
Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan.
J Physiol Anthropol. 2014 Dec 22;33(1):38. doi: 10.1186/1880-6805-33-38.
Non-shivering thermogenesis (NST) involves a substantial amount of energy expenditure in humans and, thus, contributes to reducing the risk for obesity. Molecular evolutionary studies have reported that SNPs in/near the uncoupling protein 3 gene (UCP3) and the regulatory associated protein of mTOR complex 1 gene (RPTOR) might influence NST and confer adaptive advantages for modern human dispersal into cold environments. In the present study, the impact of these SNPs on obesity-related traits was investigated.
Study subjects consisted of 2,834 Japanese adults (percentage of female: 46%, mean age: 51.5). Associations of the UCP3-55C/T and the RPTOR-26934C/T - the 2 potential genetic variations involved in cold adaptation and thermogenic mechanisms in mammals, with quantitative obesity-related traits including body mass index (BMI), waist circumference, visceral fat area (VFA), VFA adjusted for BMI, and selected blood parameters - were tested using multiple linear regression models. Sliding windowsampling analysis was applied to depict seasonal effects of the SNPs on the obesity-related phenotypes.
UCP3-55C/T and the RPTOR-26934C/T did not show any association with obesity traits and blood chemical parameters in multiple linear regression models consisting of the whole subjects. Moreover, sliding window sampling-based association analyses involving seasonality also failed to find associations between these two SNPs and obesity-related traits.
UCP3-55C/T and the RPTOR-26934C/T may only have subtle effects on the development of obesity-related traits in the present humans. These two SNPs might be irrelevant to inter-individual variations in energy metabolism and efficiency of NST.
非颤抖性产热（NST）在人类中涉及大量能量消耗，因此有助于降低肥胖风险。分子进化研究报告称，解偶联蛋白3基因（UCP3）和mTOR复合物1调节相关蛋白基因（RPTOR）中的单核苷酸多态性（SNP）可能影响NST，并为现代人类向寒冷环境扩散带来适应性优势。在本研究中，调查了这些SNP对肥胖相关性状的影响。
研究对象包括2834名日本成年人（女性比例：46%，平均年龄：51.5岁）。使用多元线性回归模型测试了UCP3 - 55C/T和RPTOR - 26934C/T这两个参与哺乳动物冷适应和产热机制的潜在基因变异与包括体重指数（BMI）、腰围、内脏脂肪面积（VFA）、经BMI调整的VFA以及选定血液参数在内的定量肥胖相关性状之间的关联。应用滑动窗口抽样分析来描述SNP对肥胖相关表型的季节性影响。
在由全体受试者组成的多元线性回归模型中，UCP3 - 55C/T和RPTOR - 26934C/T与肥胖性状和血液化学参数均无关联。此外，基于滑动窗口抽样的涉及季节性的关联分析也未发现这两个SNP与肥胖相关性状之间存在关联。
UCP3 - 55C/T和RPTOR - 26934C/T可能仅对当前人类肥胖相关性状的发展有微妙影响。这两个SNP可能与个体间能量代谢差异和NST效率无关。
