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Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation.

ABSTRACT: BACKGROUND:New-onset diabetes after transplantation (NODAT) is a serious complication in transplant recipients. Transcription factor-7-like 2 (TCF7L2) is a Wnt signaling-associated transcription factor that plays an important role in ?-cell proliferation and insulin secretion. The association between TCF7L2 SNP rs7903146 and NODAT was documented in renal transplant patients. OBJECTIVE:To determine the association between TCF7L2 rs7903146 variants and the risk of NODAT after liver transplantation. METHODS:This study was conducted on 140 liver transplant recipients who had received tacrolimus-based immunosuppressive drugs. The patients were divided into NODAT (n=70) and non-NODAT (n=70) groups and were genotyped using PCR-RFLP. In addition, 100 normal subjects were considered as the comparison group. RESULTS:There was a significant difference (p<0.05) between the two study groups regarding donor and recipient age, recipient body mass index, and recipient fasting plasma glucose before the transplantation. No significant relationship was observed between TCF7L2 rs7903146 genotypes and development of NODAT. No significant difference was also found between the two groups in terms of the tacrolimus and mycophenolate mofetil daily dosage as well as tacrolimus blood level. However, the prednisolone daily dosage was significantly (p=0.01) higher in the NODAT group compared to those without NODAT. The majority of the patients in the NODAT group also had an episode of acute rejection. Furthermore, a significant difference was found between the transplant recipients and the comparison subjects regarding T allele (p<0.001, OR=1.96) and TT genotype (p<0.001, OR=3.47) frequencies. CONCLUSION:No correlation was found between TCF7L2 genotypes and development of NODAT. Acute rejection and prednisolone pulse therapy predisposed the susceptible patients to NODAT.

SUBMITTER: Musavi Z

PROVIDER: S-EPMC4346459 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation.

Musavi Z Z Azarpira N N Sangtarash M H MH Kordi M M Kazemi K K Geramizadeh B B Malek-Hosseini S A SA

International journal of organ transplantation medicine 20150101 1

<h4>Background</h4>New-onset diabetes after transplantation (NODAT) is a serious complication in transplant recipients. Transcription factor-7-like 2 (TCF7L2) is a Wnt signaling-associated transcription factor that plays an important role in β-cell proliferation and insulin secretion. The association between TCF7L2 SNP rs7903146 and NODAT was documented in renal transplant patients.<h4>Objective</h4>To determine the association between TCF7L2 rs7903146 variants and the risk of NODAT after liver ...[more]

PMID: 25737773

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Project description:BackgroundThere are racial and ethnic differences in the prevalence of gestational diabetes mellitus (GDM). Prior meta-analyses included small samples and very limited non-Caucasian populations. Studies to determine the relationship between transcription factor 7 like-2 (TCF7L2) rs7903146 polymorphism and risk of GDM in Hispanics/Latinos are recently available. The present meta-analysis was to estimate the impact of allele variants of TCF7L2 rs7903146 polymorphism on GDM susceptibility in overall population and racial/ethnic subgroups.MethodsLiterature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test.ResultsA total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies.ConclusionsThis meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.

Project description:ObjectiveThe type 2 diabetes-associated alleles at the TCF7L2 locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the TCF7L2 locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.Research design and methodsWe evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2% white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage disequilibrium with rs7903146). Altogether, 62.6% participants carried ≥1 risk allele. Univariate and multivariable Cox proportional hazards models and Kaplan-Meier statistical methods were used.ResultsDuring follow-up (median 5.2 years, range 0.2-12.6), 62% of the single autoantibody-positive participants developed multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not significantly predict progression to multiple autoantibody positivity. However, among single GAD65 autoantibody-positive participants (n = 158), those who carried ≥1 risk allele had a lower rate of progression to multiple autoantibody positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2 or insulin autoantibody positive only, carrying ≥1 TCF7L2 risk allele was not a significant factor overall, but in overweight or obese participants, it increased the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016) even with adjustment for age.ConclusionsThe type 2 diabetes-associated TCF7L2 locus influences progression of islet autoimmunity, with differential effects by autoantibody specificity and interaction by obesity/overweight.

Dataset Information

Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation.

Publications

Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation.

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