title: The Role of TCF7L2 rs7903146 in Diabetes After Kidney Transplant: Results From a Single-Center Cohort and Meta-Analysis of the Literature.
abstract: BACKGROUND
  Several genetic polymorphisms modulate the risk of posttransplant diabetes mellitus (PTDM), a complication associated with an increased morbidity and mortality after kidney transplantation; however, their clinical utility is still undefined.
  
  
  METHODS
  Genetic analysis was performed in 464 kidney transplantation recipients to evaluate whether transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism is associated with the risk of PTDM and a meta-analysis of similar studies including our results was performed (total kidney transplantation recipients, n = 3105). A predictive model of PTDM was built on the basis of this polymorphism and clinical parameters.
  
  
  RESULTS
  In our cohort, 163 patients possessed the CC genotype of rs7903146 (35.1%), 237 were CT (51.1%), and 64 were TT (13.8%): their 2 years PTDM incidence was, respectively, 7.8%, 11.9%, and 22.7%. At multivariate analysis, age (per year; hazard ratio [HR], 1.029; 95% confidence interval [95% CI], 1.005-1.054; P = 0.017), body mass index (25.0-29.9 vs <25.0; HR, 2.43; 95% CI, 1.40-4.23; P = 0.0018; ≥30 vs <25.0; HR, 5.70; 95% CI, 2.77-11.74; P < 0.0001), TCF7L2 rs7903146 (per each T allele; HR, 1.81; 95% CI, 1.26-2.59; P = 0.001) and previous transplants (HR, 2.80; 95% CI, 1.39-5.64; P = 0.004) emerged as independent predictive factors for PTDM.Meta-analysis of present and 5 previous studies showed higher risk of PTDM in carriers of rs7903146 TT genotype (odds ratio, 1.95; 95% CI, 1.39-2.74; P < 0.0001) and absence of heterogeneity among studies (I = 0%).Inclusion of this polymorphism in a predictive model appeared to improve its ability to stratify patients according to the risk of PTDM.
  
  
  CONCLUSIONS
  In renal transplant patients, TCF7L2 rs7903146 is strongly and independently associated with PTDM and might hold the potential to identify patients at risk for this complication.
authors.affiliation: 1 Nephrology and Kidney Transplant Unit, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.2 Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale, Novara, Italy.3 Unit of Medical Statistics and Cancer Epidemiology, University of Eastern Piedmont and CPO Piemonte, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Terrazzino
authors.forename: Claudio
authors.initials: C
authors.lastname: Musetti
authors.forename: Sarah
authors.initials: S
authors.lastname: Cargnin
authors.forename: Guido
authors.initials: G
authors.lastname: Merlotti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cena
authors.forename: Piero
authors.initials: P
authors.lastname: Stratta
authors.forename: Armando
authors.initials: A
authors.lastname: Genazzani
mesh_terms: D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein