Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus.
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ABSTRACT:
SUBMITTER: Ding W
PROVIDER: S-EPMC5842570 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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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.
| S-EPMC4825985 | biostudies-literature
Project description:AIMS/INTRODUCTION:Studies have been carried out to evaluate the correlation between TCF7L2 genetic polymorphisms and gestational diabetes mellitus (GDM) risk. However, the conclusions from these studies are incomplete, because partial single nucleotide polymorphisms (SNPs) were analyzed. We carried out a meta-analysis aimed to systematically evaluate TCF7L2 gene polymorphisms and GDM susceptibility in all population and racial/ethnic subgroups to afford a foundation for future research. MATERIALS AND METHODS:Published studies censoring TCF7L2 variants and GDM risk were captured from the EMBASE, PubMed, CNKI and Wanfang databases. The meta-analysis was processed using software of RevMan 5.2 and Stata13. The relationship between TCF7L2 polymorphism and GDM occurrence was evaluated by pooled odds ratios. Stratified analysis based on race/ethnicity was also carried out. The allele-specific odds ratios and 95% confidence intervals were counted, and based on homogeneity evaluated using the I2 -test, fixed- or random-effects pooled measures were selected. RESULTS:A total of 22 studies were covered, capturing eight TCF7L2 SNPs and involving 5,573 cases and 13,266 controls. Six of eight SNPs showed significant relationships with GDM occurrence, of which the SNPs rs7903146, rs12255372 and rs7901695 were the most powerful. Stratified analysis by race/ethnicity showed discrepant results in these three SNPs. In Caucasians and other races, all these SNPs were found to have a significant association with GDM risk, but in Asians, only SNP rs7903146 showed a significant association. CONCLUSIONS:Six of eight SNPs were found to have significant associations between TCF7L2 variants and GDM risk in the overall population, with the most powerful in SNPs being rs7903146, rs12255372 and rs7901695, but the contribution of these SNPs to GDM risk were variable among different racial/ethnic groups.
| S-EPMC5497039 | biostudies-literature
Project description:The genetic predispositions responsible for developing type 2 diabetes mellitus (T2DM) in the Middle East are poorly understood. The rs7903146 single nucleotide polymorphism (SNP) located in transcription factor 7-like-2 (TCF7L2) gene has been recognized to have a vital role in the development of T2DM disorder. The current study is the first to have researched the possible association between TCF7L2 rs7903146 SNP and T2DM among Kurdish population in Kurdistan region of Iraq. The study included 212 participants, half of them were T2DM patients, and the other half were disease-free and normoglycemic controls. Genotyping was performed by using a high throughput cost and time effective tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS-PCR) assay. The rs7903146 genotypic frequencies for CC, CT and TT were 24.5%, 69.8%, and 5.7% in T2DM group respectively, and for the controls were 45.3%, 50.9%, and 3.8% respectively. The frequency of CT genotype was found significantly higher in the cases when compared to the controls (OR = 2.53, 95% CI 1.40-4.57, P value < 0.0019), which indicated that the genotype CT showed risk with diabetes. The T allele showed a high significant frequency in the patients compared to the controls (OR = 1.65, 95% CI 1.10-2.47, P value = 0.014). Our findings demonstrated that the T allele could be a risk factor for increasing the susceptibility of T2DM incidence among the Iraqi Kurdish population.
| S-EPMC8215002 | biostudies-literature
Project description:BackgroundData on the genetic variants for type 2 diabetes mellitus (T2DM) in sub-Saharan African populations are very scarce. This study aimed to investigate the association of transcription factor 7-like (TCF7L2) with T2DM in a Cameroonian population and explore possible genotype-phenotype correlation.MethodsThis is a case-control study involving 37 T2DM patients and 37 non-diabetic volunteers of Cameroonian ethnicity aged 40 years old and above. We collected clinical and biological data to determine phenotypic traits. TCF7L2 was analyzed by genotyping for rs7903146 (C/T) using PCR-RFLP. Biochemical analyses were performed using a spectrophotometer with Chronolab kits. Statistical analyses were carried out using IBM SPSS, PS and Quanto.ResultsTCF7L2 was associated with T2DM in this Cameroonian population (p = 0.013 for alleles, and p = 0.013 for genotypes). The risk allele was C (9.5% patients vs. 0% healthy controls, OR = 16.56) and the protective allele was T (90.5% patients vs. 100.0% healthy controls, OR = 0.06). The risk genotype was C/T (18.9% patients vs. 0% healthy controls, OR = 18.44), while the protective genotype was T/T (81.1% patients vs. 100.0% healthy controls, OR = 0.054). The statistical power was 99.99%. TCF7L2 was not preferentially associated with a specific disease phenotype.ConclusionTCF7L2 is associated with T2DM in this Cameroonian population. The association is not dependent on a specific T2DM phenotype. Clinical genetic testing for TCF7L2 can help to predict the occurrence of T2DM in Cameroon.
| S-EPMC4403887 | biostudies-literature
Project description:Background:Some genetic association studies tried to investigate potential associations of Transcription Factor 7 Like 2 (TCF7L2) rs7903146 polymorphism with type 2 diabetes mellitus (T2DM). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between TCF7L2 rs7903146 polymorphism and T2DM in a larger pooled population. Methods:Systematic literature research of PubMed, Web of Science and Embase was performed to identify eligible studies for pooled analyses. I2 statistics were employed to assess between-study heterogeneities. If I2 was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses. Results:Totally 68 studies with 115,809 subjects were included for analyses. The pooled analyses showed that TCF7L2 rs7903146 (dominant model: p?<?0.0001; recessive model: p?<?0.0001; over-dominant model: p?<?0.0001; allele model: p?<?0.0001) polymorphism was significantly associated with susceptibility to T2DM in overall population. Further subgroup analyses revealed similar significant findings in both Asians and Caucasians. Conclusions:In conclusion, our findings supported that TCF7L2 rs7903146 polymorphism could be used to identify individuals at high risk of developing T2DM in Asians and Caucasians.
| S-EPMC6612193 | biostudies-literature
Project description:In recent years, it has been widely accepted that transcription factor 7-like 2 (TCF7L2) is associated with type 2 diabetes mellitus (T2DM) in multiple ethnic groups, especially its single nucleotide polymorphisms of rs7903146C/T, rs12255372G/T and rs290487T/C. However, the results previously obtained in Chinese Han population are often inconsistent. For clearing this issue, herein we performed meta-analysis based on the reports that can be found to assess the association. In the meta-analysis, Odds ratio (OR) and 95% confidence interval (95% CI) were calculated with random-effect model or fixed-effect model based on the heterogeneity analysis. The quality of included studies was evaluated by using the Newcastle-Ottawa Scale. The sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. In total, 20 case-control studies with 9122 cases of T2DM and 8017 controls were included. Among these case-control studies, we selected 13 ones on rs7903146 C/T, 5 ones on rs12255372 G/T, 8 ones on rs290487 T/C. The results indicated that rs7903146C/T polymorphism was significantly associated with T2DM (T vs. C, OR = 1.73, 95% CI = 1.39-2.16). There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88-3.56; C vs. T, OR = 1.08, 95% CI = 0.93-1.25). Subgroup analysis of different regions proved the relationship between rs7903146C/T polymorphism and T2DM risk in both the northern and the southern China. The association of rs290487 with T2DM was affected by body mass index, whereas the association of rs7903146 and rs290487 with T2DM was influenced neither by age nor by sex. In conclusion, this study indicated that the rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on T2DM risk in Chinese Han population, with rs12255372G/T and rs290487T/C polymorphisms showing no significant effect.
| S-EPMC3602305 | biostudies-literature
Project description:Our objective was to evaluate the association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus (T2DM) in the world population. We carried out a survey of the literature about the effect of rs12255372 on genetic susceptibility to T2DM by consulting PubMed, the Cochrane Library, and Embase from 2006 to 2012, and then performed a meta-analysis of all the studies in order to evaluate the association between rs12255372 and T2DM. A total of 33 articles including 42 studies (with 34,076 cases and 36,192 controls) were confirmed to be eligible and were included in the final meta-analysis: 6 studies conducted on Europeans, 14 on Caucasians, 17 on Asians, 2 on Africans, and 3 on Americans. Overall, the effect size was as follows: for the variant allele T (OR = 1.387, 95%CI = 1.351-1.424), for the TT genotype (OR = 1.933, 95%CI = 1.815-2.057), for the GT genotype (OR = 1.363, 95%CI = 1.315-1.413), for the dominant model (OR = 1.425, 95%CI = 1.344-1.510), and for the recessive model (OR = 1.659, 95%CI = 1.563-1.761). In summary, by pooling all available qualified data from genetic studies on rs12255372 and T2DM, we have confirmed that rs12255372 is significantly associated with susceptibility to T2DM in the global population.
| S-EPMC3854403 | biostudies-literature
Project description:BackgroundTranscription factor 7-like 2 Protein (TCF7L2) has a strong role in the pathogenesis of type 2 diabetes mellitus (T2DM). Association between rs7903146 and T2D risk reported in some of populations. Also many loci such as UBE2Z rs46522 are affecting by TCF7L2 transcription factor have been found associated with T2D. The present study aimed to evaluate association of the SNPs with risk of T2D among our population.MethodsThis case-control study was conducted on 150 T2D patients and 150 healthy people (as a control group) in south western Iran. Genotyping was performed by PCR-RFLP.ResultsThe frequency of genotypes showed no remarkable difference between T2DM patients and control group. The odds ratios of rs7903146 (C/T) polymorphism for CC and TC genotypes were 1.9 (95% CI, 0.85 to 4.24; P=0.12) and 0.81 (95% CI, 0.47 to 1.38; P=0.43) compared with the TT genotype, respectively. The odds ratios of rs46522 (C/T) polymorphism for TT and TC genotypes were 1.75 (95% CI, 0.86 to 3.59; P=0.13) and 1.38 (95% CI, 0.81to 2.35; P=0.24) compared with the CC genotype, respectively.ConclusionOur study indicates no association of T2D in south western Iran with the rs7903146 and rs46522 variants.
| S-EPMC7040290 | biostudies-literature
Project description:The transcription factor 7-like 2 gene (TCF7L2) rs7903146 T allele is constantly associated with Type 2 diabetes in various populations and ethnic groups. Nevertheless, this has not been observed in two studies involving Arab populations. The aim of the present study was to investigate the association between TCF7L2 rs7903146 in an Iranian population. Type 2 diabetes patients (N = 258) and normal healthy control subjects (N = 168) from the same area, were examined. The ARMS- PCR (Amplification Refractory Mutation System) technique, subsequently validated by direct sequencing, was used for genotyping. Allele and genotype frequencies were significantly different between patients and controls TT vs. CT + CC [p 0.0081 OR 3.4 95%CI (1.27-11.9)] and T vs. C allele [p 0.02 OR 1.4 95%CI (1.03-1.9)]. Our data thus confirm the association between the rs7903146 T allele and T2D in an Iranian population, contrary to previous reports in Arab populations. This can possibly be attributed to differences in ethnic background or the effects of environmental factors.
| S-EPMC3036108 | biostudies-literature
Project description:BACKGROUND: The transcription factor 7-like 2 (TCF7L2) gene is the most significant genetic risk factor for type 2 diabetes (T2D). Association analyses were performed on participants (n = 751, aged between 30 and 64) in the ISOR population-based study in the city of Oran. Dietary intakes were estimated using a weekly food frequency questionnaire. RESULTS: The T allele of the rs7903146 single nucleotide polymorphism (SNP) was associated with lower body weight (p = 0.02), lower BMI (p = 0.009), lower waist circumference (p = 0.01) and a lower waist-to-hip ratio (p = 0.02). The T allele was associated with a significantly higher risk of T2D (odds ratio (OR) (95% confidence interval) = 1.55 (1.09-2.20), p = 0.01) and this association was independent of BMI. When considering the T2D risk, there were nominal interactions between the rs7903146 SNP and dessert (p = 0.05) and milk intakes (p = 0.01). The T2D risk was greater in T allele carriers with high dessert and milk intakes (OR = 2.61 (1.51-4.52), p = 0.0006, and 2.46 (1.47-4.12), p = 0.0006, respectively). In subjects with a high dessert intake, the T allele was also associated with higher fasting plasma glucose concentrations (4.89 ± 0.46 mmol/L in TT subjects, 4.72 ± 0.48 mmol/L in CT subjects and 4.78 ± 0.51 mmol/L in CC subjects; p = 0.03). CONCLUSIONS: The T allele of the rs7903146 SNP is associated with a significantly higher risk of T2D in an Algerian population. This association was further strengthened by a high dessert intake, suggesting that gene-diet interactions increase the T2D risk.
| S-EPMC4266211 | biostudies-literature