title: Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan. nakayama@jichi.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyashita
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000076223:Regulatory-Associated Protein of mTOR; D000071247:Uncoupling Protein 3; D055105:Waist Circumference
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007473:Ion Channels; D024101:Mitochondrial Proteins; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D002784:Cholesterol