title: An adaptive variant of TRIB2, rs1057001, is associated with higher expression levels of thermogenic genes in human subcutaneous and visceral adipose tissues.
abstract: BACKGROUND
  An obesity-related single-nucleotide polymorphism (SNP) of the Tribbles pseudokinase 2 gene (TRIB2) was shown to have underwent adaptive evolution in the last glacial period, suggesting a selective advantage of this SNP in human populations in cold environments. In order to verify this hypothesis, the effect of the TRIB2 SNP on the expression of genes involved in adaptive thermogenesis was tested using messenger RNAs prepared from adipose tissues of Japanese adults.
  
  
  METHODS
  Complementary DNA was prepared from subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) obtained from 48 Japanese adults. Transcript levels of 15 selected genes, including five genes that are upregulated in development of thermogenic adipocytes, were measured by using real-time polymerase chain reaction. Differences in transcript levels between the TRIB2 SNP genotype groups (AA genotype versus AT + TT genotype) were assessed using t test.
  
  
  RESULTS
  Of the five thermogenic genes, DIO2, CIDEA, PPARGC1A, and PRDM16 showed significantly higher transcript levels in SAT of individuals with the AA genotype relative to those with the AT + TT genotype (P < 0.05). However, only 2 out of the 10 non-thermogenic genes exhibited differences in transcript levels according to genotype. Additionally, in silico prediction indicated that this SNP likely affects the expression of nearby genes including TRIB2.
  
  
  CONCLUSIONS
  The higher expression levels of thermogenic genes in individuals homozygous for the adaptive variant of TRIB2 SNP suggest a greater propensity for induction of thermogenesis in adipose tissues in cold environments.
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan. nakayama@jichi.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan.
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D000328:Adult; D044466:Asian People; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008297:Male; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism*; D022722:Thermogenesis / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human
keywords: Obesity; SNP; TRIB2; Thermogenesis