title: Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects.
abstract: OBJECTIVE
  The prevalence of type 2 diabetes mellitus (DM) among Emirati subjects is one of the highest in the world. This has been attributed to rising prevalence of obesity acting on genetically susceptible individuals. We analyzed the associations between TCF7L2 polymorphism and DM, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects.
  
  
  METHODS
  We genotyped the two TCF7L2 single nucleotide polymorphisms (SNPs) rs12255372 and rs7903146 in 368 adult subjects. Homeostatic model assessment (HOMA) was used to assess beta cell function (HOMA2-%B) and insulin resistance (HOMA2-IR). The SNP genotypes were analyzed against disease stage [normal glucose=0 (n=188), pre-diabetes=1 (n=85), and DM=2 (n=95)] and against clinical and biochemical measures. Age and sex were included as covariates in all association analyses. Additional adjustments were made for body mass index (BMI) and waist circumference in several analyses.
  
  
  RESULTS
  Diabetes disease stage was marginally significantly associated with the frequency of the T variant at rs12255372 (p=0.057; adjusted p=0.017) but not at rs7903146 (p=0.5; adjusted p=0.2). Comparison between subjects with normal glucose and the combined DM/pre-diabetes showed a significant association with rs12255372 (OR 1.47, CI 1.04-2.08; p=0.03) but not with rs7903146 (OR 1.16, CI 0.81-1.64; p=0.4). We found no association with metabolic syndrome, or with insulin and glucose levels, HOMA2-%B or HOMA2-IR. The age-standardized prevalence rate for metabolic syndrome was 43.9% in men and 42.1% in women.
  
  
  CONCLUSIONS
  These data suggest that TCF7L2 variants are associated with increased risk for DM in Emirati subjects. We also demonstrate a high prevalence of the metabolic syndrome in this population.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, United Arab Emirates. saadih@uaeu.ac.ae
authors.forename: Hussein
authors.initials: H
authors.lastname: Saadi
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Nagelkerke
authors.forename: S George
authors.initials: SG
authors.lastname: Carruthers
authors.forename: Sheela
authors.initials: S
authors.lastname: Benedict
authors.forename: Samar
authors.initials: S
authors.lastname: Abdulkhalek
authors.forename: Richard
authors.initials: R
authors.lastname: Reed
authors.forename: Miodrag
authors.initials: M
authors.lastname: Lukic
authors.forename: M Gary
authors.initials: MG
authors.lastname: Nicholls
mesh_terms: D000328:Adult; D000368:Aged; D018912:Arabs / Q000235:genetics; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014479:United Arab Emirates / Q000453:epidemiology
chemical_list: D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein