Dataset Information

Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort.

ABSTRACT: OBJECTIVE:To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control. RESEARCH DESIGN AND METHODS:Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort. RESULTS:At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for beta-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35-3.20] and 3.56 [2.11-5.98] in CT and TT genotypes, respectively). CONCLUSIONS:The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.

SUBMITTER: Gambino R

PROVIDER: S-EPMC2875429 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort.

Gambino Roberto R Bo Simona S Gentile Luigi L Musso Giovanni G Pagano Gianfranco G Cavallo-Perin Paolo P Cassader Maurizio M

Diabetes care 20100318 6

<h4>Objective</h4>To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control.<h4>Research design and methods</h4>Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort.<h4>Results</h4>At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for beta-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fastin ...[more]

PMID: 20299486

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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:BACKGROUND:A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has been found to be associated with type 2 diabetes in case-control studies. We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population. METHODS:In total, 944 subjects aged > or = 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of > or = 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were > or = 5.6 mmol/l to < 7 mmol/l. RESULTS:In the general population sample, minor (T) allele carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting poorer beta-cell function. T allele carriers also had smaller waist circumference (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4% in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T allele carriers had metabolic syndrome features (p = 0.047) or had experienced a myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024). CONCLUSION:The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population. Patients with diabetes who are carriers of the minor allele are less likely to have metabolic-syndrome features, but may experience more microvascular complications, although the number of cases was small. If replicated, these findings may have implications for developing treatment approaches tailored by genotype.

Dataset Information

Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort.

Publications

Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort.

Similar Datasets

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