title: The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study.
abstract: OBJECTIVE
  The variants of transcription factor 7-like 2 (TCF7L2) gene have been proposed to be associated with latent autoimmune diabetes in adults (LADA). We sought to confirm the possible association in Europeans and to examine the interaction between one gene variant and clinical data.
  
  
  METHODS
  The TCF7L2 rs7903146 C-to-T polymorphism was genotyped in 211 LADA, 1,297 type 2 diabetic, 545 type 1 diabetic and 1,497 control individuals from Hungary. A meta-analysis of our and previously published studies was performed to evaluate the size and the heterogeneity of the gene effect.
  
  
  RESULTS
  The meta-analysis yielded a significant effect of TCF7L2 T allele (OR 1.28; p < 0.0001) on LADA risk without heterogeneity among Europeans. The T allele conferred equally strong susceptibility to LADA and type 2 diabetes. In the Hungarian dataset, the T allele was associated with LADA and type 2 diabetes, but not with type 1 diabetes. T allele carriers had significantly lower BMI than patients with the CC genotype in the LADA and type 2 diabetes groups (p = 0.0021 and p = 0.0013, respectively). In both diseases, the diabetes risk was significantly higher in the non-overweight than in the overweight BMI category (p = 0.0013 and p < 0.0001, respectively); susceptibility to LADA was increased by 2.84-fold in non-overweight individuals compared with overweight ones.
  
  
  CONCLUSIONS
  The meta-analysis demonstrates that TCF7L2 rs7903146 polymorphism is a population-independent susceptibility locus for LADA in Europeans. The effect size is similar for LADA and type 2 diabetes. The gene effect on diabetes risk may be modulated by BMI, such that the lower the BMI, the higher the gene effect.
authors: 1st Department of Paediatrics, Semmelweis University, Bókay u 53-54, 1083 Budapest, Hungary. krisztinalukacs@hotmail.com
authors: K
authors: K
authors: Lukacs
authors: N
authors: N
authors: Hosszufalusi
authors: E
authors: E
authors: Dinya
authors: M
authors: M
authors: Bakacs
authors: L
authors: L
authors: Madacsy
authors: P
authors: P
authors: Panczel
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005060:Europe; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D050177:Overweight / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein