Investigation of polymorphisms rs7903146 and rs12255372 in the TCF7L2 gene in biochemical markers of severity of type 2 diabetes mellitus (T2DM) in a sample of adults with T2DM
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SUBMITTER: Dal Bosco S
PROVIDER: S-EPMC4204211 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:Background and aimsMetabolic abnormalities in T2DM (Type 2 diabetes mellitus) include classic manifestations such as impaired insulin secretion, synthesis and peripheral insulin resistance. The intronic variants rs7903146 and rs12255372 of the TCF7L2 (transcription factor 7-like 2) gene are strongly associated with risk of incidence of T2DM and impaired β-cell functions. Studies addressing the early T2DM onset, and early insulin dependence in T2DM patients of south Tamil Nadu are still lacking, and hence the present study focuses in determining the influence of the TCF7L2 polymorphisms in the incidence and disease course in the T2DM patients of south Tamil Nadu.MethodsAnthropometric measurements and biochemical parameters were carried out in early onset (Group A), early onset insulin dependent T2DM patients (Group B) and non-insulin dependent T2DM patients (Group C). PCR, allele specific PCR (ASP), PCR product sequencing strategies were utilized to determine the genotype and the impact of the TCF7L2 SNPs in the T2DM disease course.ResultsFemale T2DM patients with the CT/TT rs7903146 genotype (P = 0.005) and the rs12255372 GT/TT genotype (P = 0.036) exhibited a significantly low mean age for T2DM incidence. Correlation/regression analysis in the T2DM patients revealed that rs12255372 (P = 0.042) is associated with early onset in the Group C patients and the rs7903146 (P = 0.018), rs12255372 (P = 0.026) are associated with insulin dependence in the group B patients.ConclusionScreening for the TCF7L2 polymorphisms will prevent T2DM incidence and enable life style changes, appropriate therapeutic strategies that would help combat the accelerated disease course in the T2DM patients.
| S-EPMC6873260 | 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:BackgroundA significant overlap in the pathophysiological features of polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) has been reported; and insulin resistance is considered a central driver in both. The expression and hepatic clearance of insulin and subsequent glucose homeostasis are mediated by TCF7L2 via Wnt signaling. Studies have persistently associated TCF7L2 genetic variations with T2DM, however, its results on PCOS are sparse and inconsistent.MethodsWe performed a comprehensive literature review of the data published till June 2024, on rs7903146, rs12255372, and PCOS in PubMed, Medline, the Cochrane Library, Google Scholar, Science Direct, Scopus, and Web of Science, followed by a meta-analysis to evaluate the association between these genetic variations and the PCOS risk. Using a random effects model, the pooled odds ratio (OR) and confidence intervals (95%CI) were computed using STATA statistical software.ResultsThe genotypic data from 3052 controls and 2291 women with PCOS from ten published studies were analysed. The results indicated no cumulative association between the rs7903146 variant and PCOS risk in either the allelic (C vs. T: OR = 1.21; 95% CI: 0.96-1.47, p > 0.05) or genotypic models (CC vs. CT + TT: OR = 1.06; 95% CI: 0.90-1.23, p > 0.05). Similarly, the genetic variant rs12255372 was not associated with PCOS risk both in the allelic and the dominant inheritance model(p > 0.05). Unlike East Asians (MAF < 0.025), both variants are highly frequent across other global populations including America, South Asia, and Europe (MAF ≥ 0.19).ConclusionUnlike T2DM, our results showed that rs7903146 and rs12255372 variants of the TCF7L2 gene do not modulate the PCOS risk. However, the role of other TCF7L2 variants remains to be studied in future studies.
| S-EPMC11702189 | biostudies-literature
Project description:BackgroundTCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects.Methods and resultstwo populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95%CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004).Conclusionsrs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.Clinical trial registration informationMEDICINE, ANGIOPLASTY, OR SURGERY STUDY (MASS II): Unique identifier: ISRCTN66068876.
| S-EPMC2773425 | 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:BackgroundLarge scale association studies have found a significant association between type 2 diabetes mellitus (T2DM) and transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146. However, the quality of data varies greatly, as the studies report inconsistent results in different populations. Hence, we perform this meta-analysis to give a more convincing result.MethodsThe articles, published from January 1st, 2000 to April 1st, 2017, were identified by searching in PubMed and Google Scholar. A total of 56628 participants (34232 cases and 22396 controls) were included in the meta-analysis. A total of 28 studies were divided into 4 subgroups: Caucasian (10 studies), East Asian (5 studies), South Asian (5 studies) and Others (8 studies). All the data analyses were analyzed by the R package meta.ResultsThe significant association was observed by using the dominant model (OR = 1.41, CI = 1.36 - 1.47, p < 0.0001), recessive model (OR = 1.58, CI = 1.48 - 1.69, p < 0.0001), additive model(CT vs CC) (OR = 1.34, CI = 1.28-1.39, p < 0.0001), additive model(TT vs CC) (OR = 1.81, CI = 1.69-1.94, p < 0.0001)and allele model (OR = 1.35, CI = 1.31-1.39, p < 0.0001).ConclusionThe meta-analysis suggested that rs7903146 was significantly associated with T2DM in Caucasian, East Asian, South Asian and other ethnicities.
| S-EPMC5842570 | biostudies-literature
Project description:In various populations worldwide, common variants of the TCF7L2 (Transcription factor 7-like 2) gene are associated with the risk of type 2 diabetes mellitus (T2DM). The aim was to investigate the association between rs12255372 (G/T) polymorphism in the TCF7L2 gene and T2DM in an Iranian population. 236 unrelated patients with T2DM, and 255 normoglycemic controls without diabetes were studied. The PCR-RFLP method was used for genotyping rs12255372 (G/T) polymorphism, and the SPSS version 18.0 for Windows for statistical analysis. The minor T allele of TCF7L2 rs12255372 was found to significantly increase the risk of T2DM, with an allelic odds ratio (OR) of 1.458 (95% CI 1.108-1.918, p = 0.007). A significant difference in TT genotype was observed between T2DM patients and normoglycemic controls (OR 2.038, 95% CI 1.147-3.623; p = 0.014). On assuming dominant and recessive models, ORs of 1.52 [95% CI (1.05-2.21) p = 0.026)] and 1.74 [95% CI (1.01-3.00) p = 0.043] were obtained, respectively, thereby implying that the co-dominant model would best fit the susceptible gene effect. This study further confirms the TCF7L2 gene as enhancing susceptibility to the development of T2DM.
| S-EPMC3389527 | biostudies-literature
Project description:BackgroundTranscription factor 7-like 2 (TCF7L2) is a transcription factor in the Wnt signaling pathway. High levels of TCF7L2 have been reported in most human tissues, including the heart, lung, brain, liver, kidney, placenta, adipose tissues, and pancreatic β-cells. The purpose of this study was to assess the association between TCF7L2 polymorphisms (rs12255372 and rs7903146) and type 2 diabetes mellitus in the city of Jahrom, Iran.MethodsThis case-control study was conducted with 200 patients referred to Diabetes Clinics and 200 healthy subjects in Jahrom City. Biochemical characteristics were first determined. TCF7L2 rs1255372 and rs7903146 polymorphisms were then genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.ResultsT-allele frequencies of both single nucleotide polymorphisms (SNPs) were significantly higher in diabetic patients than in normal glucose-tolerant subjects (rs12255372: 20.3% vs. 14.5%; rs7903146: 28.5% vs. 22.25%). The rs12255372 (G/T) polymorphism analysis showed an odds ratio of 0.473 (95% confidence interval [CI], 0.170 to 1.314; P=0.151) for the TT genotype and 0.646 (95% CI, 0.410 to 1.019; P=0.060) for the TG genotype, compared with the GG genotype. The rs7903146 (C/T) polymorphism odds ratios for TT and TC genotypes were 0.564 (95% CI, 0.280 to 1.135; P=0.109) and 0.751 (95% CI, 0.487 to 1.157; P=0.194) compared with the CC genotype, respectively.ConclusionThe rs12255372 and rs7903146 SNPs of the TCF7L2 gene were not associated with insulin resistance in the evaluated population.
| S-EPMC4696988 | biostudies-literature
Project description:BackgroundTo study the relationship between the rs12255372 (G/T) polymorphism of the transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in a Cameroonian population.MethodsThis case-control study included 60 T2DM patients and 60 healthy normoglycemic controls, all unrelated and of Cameroonian origin, aged above 40 years (range 40-87). The Restriction Fragment Length Polymorphism - Polymerase Chain Reaction (RFLP-PCR) was used for genotyping.ResultsThe T allele frequency was significantly higher in the diabetic group (0.44) than in the control group (0.17). This allele was significantly associated to a greater risk of developing T2DM as compared to the G allele (OR = 3.92, 95% CI 2.04 - 7.67, p < 0.0001). The codominant (additive) model explained best the risk of developing the disease, as the TT genotype was significantly associated to T2DM when compared to the GG genotype (OR = 4.45, 95% CI 1.64 - 12.83, p = 0.0014). By logistic regression adjusted for age, this OR was 4.33 (95% CI: 1.57 - 11.92, p = 0.005).ConclusionOur findings suggest that the rs12255372 (G/T) polymorphism of the TCF7L2 gene is an important risk factor for T2DM in the Cameroonian population.
| S-EPMC4434239 | 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