Transcription Factor 7-like 2 Rs7903146 Research Articles

Association of TCF7L2 Variants in Type 2 Diabetes Mellitus with Hypertriglyceridemia - A Case-Control Study.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition involving various genetic and environmental factors leading to impaired insulin secretion, resulting in hyperglycemia. The transcription factor 7-like 2 (TCF7L2) gene is an element of the Wnt signaling pathway that plays an important role in glucose and lipid metabolism. The aim of this study is to evaluate the association of TCF7L2 rs7903146 and rs12255372 polymorphisms in T2DM with hypertriglyceridemia. We investigated the effect of rs7903146 and rs12255372 on T2DM with high triglyceride (TG) levels in 60 patients and 20 controls. The anthropometric measurements and biochemical tests were assessed. Peripheral blood samples were collected, and genomic DNA was extracted. The genotyping of TCF7L2 polymorphisms was carried out using polymerase chain reaction (PCR)-based direct sequencing and allele-specific PCR methods. The T2DM patients and controls were compared by means of the t-test, Chi-square test, odds ratio (OR), and 95% confidence interval (CI) using Epi Info v7. The HbA1c was found to be 9.7 ± 2.1 and 5.4 ± 0.5% in patients and controls, respectively. The average TG levels (P < 0.005) in patients were 205.2 ± 145.7 and 106.4 ± 27.4mg/dl in controls. Significant evidence of association was found in T2DM patients having high TG levels with rs7903146 CT/TT (OR: 4.89; P = 0.0105) and rs12255372 GT/TT (OR: 5.23; P = 0.0101) genotypes when compared to controls. The results of this study show that TCF7L2 rs7903146 CT/TT and rs12255372 GT/TT genotypes are significantly associated with the risk of hypertriglyceridemia in individuals with T2DM among the studied population.

Association between TCF7L2 polymorphism and type 2 diabetes mellitus susceptibility: a case-control study among the Bangladeshi population.

Diabetes is a severe health burden for Bangladesh. Genetic polymorphism has been reported to be one of the major risk factors for diabetes in various studies. TCF7L2 (transcription factor 7 like 2) transcripts in the human β-cell have effects on β-cell survival, function, and Wnt signaling activation. This study aimed to evaluate the frequency and association of various polymorphisms namely TCF7L2 rs12255372 and rs7903146 among Bangladeshi patients with T2DM (Type 2 Diabetes Mellitus). This case-control study included 300 patients with T2DM and 234 healthy individuals from two health facilities in the Chattogram Division of Bangladesh. Anthropometric measurements were assessed using a self-reported, structured, eight-item questionnaire. The polymorphisms were identified by PCR-RFLP and sequencing method. A strong association of T2DMwith polymorphisms was observed, including rs12255372 (p = 0.0004) and rs7903146 (p = 0.005). It was observed that the risk genotype at rs12255372 was associated with age (p = 0.009), a family history of diabetes (p < 0.0001), and HbA1C (p < 0.0001). Furthermore, it was found that rs12255372 was substantially associated with hypertension (p = 0.03), eye problems (p = 0.01), and neurological abnormalities (p = 0.02). This study postulates that TCF7L2 genetic polymorphism is associated with the risk of T2DM among thestudied Bangladeshi population. The findings should be replicated through more studies with a large number of samples and in different populations.

Association between Transcription Factor 7-Like 2 C/T Polymorphism and Diabetic Retinopathy Risk: A Meta-Analysis

Background: Previous studies have suggested a close association between transcription factor 7-like 2 (TCF7L2) polymorphisms and diabetic retinopathy (DR) susceptibility. However, the published results were inconsistent. This meta-analysis was conducted to review and examine the relationship between TCF7L2 rs7903146 C/T polymorphism and DR risk. Materials and Methods: Online databases were searched, and the related studies were identified in this meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power. Moreover, heterogeneity test, sensitivity accumulative analysis, and publication bias were conducted to measure the statistical effect. Result: 6 studies involving 12,982 subjects were included in this meta-analysis to assess the association between rs7903146 C/T polymorphism and DR susceptibility. The synthetic results indicated that the mutation of rs7903146 C/T polymorphism maybe accompanied with an increased risk for DR (T vs. C: OR = 1.26, 95% CI = 1.00–1.60, p = 0.05, I2 = 83.5%; TT vs. CC: OR = 1.79, 95% CI = 1.12–2.86, p = 0.02, I2 = 80.2%; TT vs. CC + CT: OR = 1.62, 95% CI = 1.38–1.92, p < 0.01, I2 = 32.3%). Moreover, the subgroup analysis also demonstrated an increasing risk for DR with T mutations in Caucasian descendants. Conclusion: The current evidences of meta-analysis suggested that the TCF7L2 rs7903146 C/T polymorphism might play an important role in DR susceptibility.

Association of the Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism with the Risk of Diabetic Nephropathy: A Meta-Analysis.

Transcription factor 7-like 2 (TCF7L2) polymorphism plays an essential role in the occurrence and development of patients living with diabetes, but the current conclusions are inconsistent on the relationship between TCF7L2 polymorphism and the risk of diabetic nephropathy. This meta-analysis aims to explore the exact association between TCF7L2 rs7903146 locus polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on the relationship between single nucleotide polymorphism at TCF7L2 rs7903146 locus and susceptibility to diabetic nephropathy until January 10, 2022. The data were analyzed by Stata 15.0 software. A total of 7 articles were included, covering 1443 patients with diabetic nephropathy and 2129 diabetic non-nephropathy patients. The results showed that allele C at TCF7L2 rs7903146 locus, compared to allele T, the pooled odds ratio (OR)=0.69 (95% CI: 0.56-0.85, p≤0.05). In the dominant gene inheritance model, recessive gene inheritance model, homozygous genetic model, and heterozygous genetic model, the pooled OR was 0.47 (95% CI: 0.36-0.61), 0.63 (95% CI: 0.54-0.73), 0.39 (95% CI: 0.29-0.51), and 0.59 (95% CI: 0.45-0.78), respectively, and the differences were statistically significant. In conclusion, TCF7L2 rs7903146 polymorphism is associated with susceptibility to diabetic nephropathy. Allele T and genotype TT can increase the risk of diabetic nephropathy.

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest.

Improvement of glycemic indices by a hypocaloric legume-based DASH diet in adults with type 2 diabetes: a randomized controlled trial.

The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. This study was a randomized controlled trial. Three-hundred participants, aged 30-65years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoproteincholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17).

Association of TCF7L2 Polymorphisms with Susceptibility to Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy with a strong genetic predisposition. GDM is associated with complications during pregnancy and increased risk of type 2 diabetes later in mothers and develops a vicious cycle of metabolic diseases for future generations. Evidence is accumulating that women with genetic variants at transcription factor 7-like 2 (TCF7L2) gene are more susceptible to GDM. The aim of the current meta-analysis was to assess the association of the TCF7L2 polymorphisms with GDM risk.&#x0D; Methods: PubMed, Web of Science, Embase, SID and CNKI databases were searched to identify relevant studies up to November 01, 2020. Using the fixed-effect or random-effect model, the pooled odds ratio and its corresponding 95% confidence interval were computed.&#x0D; Results: A total of 38 case-control studies including 24 studies with 6021 cases and 13289 controls on rs7903146, eight studies with 2404 cases and 2615 controls on rs12255372 and six studies with 1357 cases and 2858 controls on rs7901695 polymorphism were selected. Pooled data showed that there was a significant association between the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms and an increased risk of GDM in whole population. Stratified analysis showed that the TCF7L2 rs7903146 polymorphism was associated with GDM in Caucasian, mixed and Chinese women, but not in Asians. Moreover, the TCF7L2 rs12255372 polymorphism was associated with GDM in Asians and Caucasians women with GDM.&#x0D; Conclusion: The combined data indicated that the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms were associated with a significant risk of GDM in whole population, especially in Caucasian women.

PPARɣ2, aldose reductase, and TCF7L2 gene polymorphisms: relation to diabetes mellitus.

Diabetes mellitus (DM) is a growing global health concern. Genetic factors play a pivotal role in the development of diabetes. Therefore, the present work aimed to study the relation between peroxisome proliferator-activate receptors (PPARɣ2) (rs3856806), aldose reductase (AR) (rs759853), transcription factor 7 like 2 (TCF7L2) (rs7903146) gene polymorphism with diabetes in the Egyptian population. The study included 260 diabetics and 120 healthy subjects. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. Regression analysis revealed that PPARɣ2 TT, TCF7L2 TT were suggested to be independent risk predictors for T1DM and TCF7L2 TC, CC genotype were suggested to be independent protective factors against T1DM development. On the other hand, PPARɣ2 TT, AR TT genotypes were suggested to be independent risk predictors for T2DM susceptibility, and PPARɣ2 CT genotypes were suggested to be independent protective factors against T2DM development. The present study revealed that PPARγ2 (rs3856806), TCF7L2 (rs7903146) and AR (rs759853) gene polymorphism may play an important role in the susceptibility of diabetes. Therefore, these polymorphisms may have a prognostic value for diabetes in the Egyptian population. Further work is required to confirm the role of these polymorphisms in diabetes.

TCF7L2 rs7903146 Is Associated With Increased Risk of New-Onset Diabetes After Transplant: A Meta-analysis of Literature

Single nucleotide polymorphisms may influence the risk of development of new-onset diabetes after transplant (NODAT), a post-transplant clinical complication that is often implicated in allograft rejection and mortality. We performed a meta-analysis of association between transcription factor 7-like-2 (TCF7L2) rs7903146 and risk of NODAT. A systematic search was conducted using PubMed and ScienceDirect electronic databases for studies published between January 2001 and January 2021. Case-control or cohort studies reporting association between NODAT (diagnosis based on American Diabetes Association criteria) and TCF7L2 rs7903146 were included. MetaGenyo was used for meta-analysis (random-effects model). Pooled odds ratios with 95% confidence intervals were reported to evaluate the strength of association. Two reviewers independently screened for articles. A total of 6 case-control studies were included for full-text review and quantitative analysis after screening for eligibility. Genotypic distributions were in Hardy-Weinberg equilibrium for included studies. All articles reported statistically significant association of TCF7L2 rs7903146 for risk of NODAT except for 1 study. There was moderate heterogeneity among studies (I2=60.6%). Pooled analysis revealed 51% odds of developing NODAT with TCF7L2 rs7903146 T allele (allele contrast model: odds ratio, 1.51; 95% confidence interval, 1.13-2.02; P=.005). The present meta-analysis demonstrated association between TCF7L2 variant rs7903146 and risk of developing NODAT. This finding suggest clinical implications for individuals undergoing kidney transplant.

Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Abstract Background Type 2 diabetes mellitus (T2DM) is a heterogeneous group of metabolic disorders characterized by the incapability of pancreatic beta cells to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multi-factorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β –catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis and the incretin glucagon-like peptide 1 (GLP-1) gene. Aim of the Work In this study we aimed to investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with type 2 diabetes mellitus. Patients and Methods The study was a case- control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non diabetic healthy controls matched with the patients in age and sex. All subjects underwent full history taking, thorough clinical examination, routine laboratory investigations including haemoglobin A1c (HbA1c), lipid profile; total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) and determination of TCF7L2 gene polymorphism by real-time quantitative polymerase chain reaction (RT-PCR). Results The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68-2.6), the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49-2.7) and the homozygous mutant genotype (TT) with OR of 3.16 (95% CI: 0.15-6.31), however, they were statistically insignificant (p-value &amp;gt;0.05). Conclusion Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM, however, it pointed to the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.

Association of TCF7L2 rs7903146 Polymorphism with Diabetic Nephropathy in Type 2 Diabe-tes Mellitus Egyptian Patients

Background: Transcription factor 7-like 2 (TCF7L2) gene polymorphisms are known risk factors for type 2 diabetes mellitus (T2DM). However, the relationship between TCF7L2 polymorphism and diabetic nephropathy (DN) is inconclusive. Objectives: to explore the association of TCF7L2 rs7903146 (C/T) gene polymorphism and DN in T2DM Egyptian patients. Methods: 80 patients with T2DM (40 patients without DN and 40 patients with DN) were enrolled in the study. Genotyping for the rs7903146 (C/T) polymorphism in TCF7L2 gene was performed by real time PCR. Results: The frequency of rs7903146 genotypes in diabetic patients without DN was ( CC: 57.5%; CT: 37.5%; TT: 5%), while in diabetic patients with DN was (CC: 2.5%; CT: 40%; TT: 57.5%). Patients with DN were exposed to the TT 25.7 times more than who didn’t develop DN (OR= 25.7, 95% CI= 0.43-94, P= 0.001**). Upon examining the allelic discrimination, C allele was present in 77.5% of patients without DN versus 23.8% of patients with DN, While T allele was found in 22.5% of patients without DN versus 76.3% of patients with DN. Patients with DN were exposed to the T allele 11 times more than who didn’t develop nephropathy (OR=11, 95% CI= 5.3-23.1 , P=<0.001**). Conclusion: rs7903146 TCF7L2 gene polymorphism may be significantly associated with the susceptibility to DN in Egyptian T2DM patients.

Interaction between TCF7L2 rs7903146 Genotype, HbA1c Levels, and the Periodontal Status of Dental Patients.

Objective The aim of the study was to investigate the potential interaction between TCF7L2 rs7903146 genotype, which is implicated for type-2 diabetes mellitus genetic susceptibility, HbA1c levels, and the periodontal status of dental patients. Materials and Methods HbA1c levels, clinical periodontal parameters (probing depth, clinical attachment level, bleeding on probing, and plaque index), and several parameters (such as body mass index [BMI], smoking habits, education level, and age) were recorded in 150 patients who fulfilled the criteria for screening for prediabetes/diabetes of the Centers for Disease Control and Prevention. DNA was extracted and the TCF7L2 single nucleotide polymorphism (SNP) rs7903146 was genotyped in all participants. Results Thirty-one patients out of 150 tested were found with unknown hyperglycemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between patients displaying HbA1c < 5.7 and ≥ 5.7% (Pearson’s Chi-square test, p > 0.05). Regarding periodontal parameters and differences between subgroups (HbA1c levels ≥ 5.7 and HbA1c levels < 5.7), statistically significant differences were observed for probing depth (3.20 ± 0.94 vs. 2.81 ± 0.78 mm), clinical attachment level (3.54 ± 1.20 vs. 3.18 ± 1.06 mm) and bleeding on probing (0.62 ± 0.25 vs. 0.50 ± 0.24%) with hyperglycemic patients exhibiting worse periodontal conditions (Mann–Whitney test p < 0.05). The allelic and genotype frequencies for the transcription factor 7-like 2 ( TCF7L2 ) gene, SNPs 7903146 did not exhibit a significant difference between the HbA1c > 5.7 and HbA1c < 5.7 groups and the periodontitis and nonperiodontitis subgroups respectively (Fisher’s exact test >0.05). Statistical Analysis Patient characteristics and their association with prediabetes were tested by Pearson’s Chi-square test (asymptotic, two sided). Differences of periodontal parameters between subgroups were tested with the Mann–Whitney U-test. The associations of allele and genotype frequencies in the patient and control groups were analyzed using the Fisher’s exact test of independence.The significance level was set at the 0.05 for all tests. Conclusion A statistically significant association between TCF7L2 rs7903146 genotype and periodontal condition or HbA1c levels was not observed in contrast to statistically significant differences of clinical parameters of periodontitis in patients with hyperglycemia.

Significant Association of Polymorphisms in the TCF7L2 Gene with a Higher Risk of Type 2 Diabetes in a Moroccan Population.

Background and aims: Several studies have shown that genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) are highly associated with the development of type 2 diabetes mellitus (T2DM) and its associated complications in several populations. The aim of our study was to investigate the association of the rs7903146 (C/T) and rs12255372 (G/T) polymorphism in the TCF7L2 gene with the risk of developing T2DM in the Moroccan population. Material and methods: A total of 150 T2DM patients and 100 healthy controls were recruited for various anthropometric, biochemical and genetic parameters. Genotyping was performed by using Real Time-PCR. The frequency of genotypes, alleles, anthropometric measures, glycemia, glycated hemoglobin (HbA1c) were evaluated in patients and control, while lipid profile was available only for T2DM group. Results: Glycemia, HbA1c and body mass index (BMI) were significantly higher in T2DM group than control. Analysis of the distribution of the TCF7L2 rs7903146 genotype and allele revealed that the TT genotype was more frequent in T2DM group (24.0%) than in healthy controls (5%) (OR = 4.08, 95% confidence interval (CI = 1.95–11.80, p < 0.0001). The T allele was more frequent in diabetic patients (45.2%) than healthy control (34.5%) and it was associated with high risk of diabetes (OR = 2.13, 95% CI = 1.12–7.31, p = 0.005). The same results were found regarding rs12255372, TT genotype frequencies were 18,7% and 6.0% in T2DM and control group, respectively (OR = 3.11, 95% CI = 1.33–7.24, p = 0.004). The T allele was over-presented in diabetics compared to controls (45.3% and 38.0%, respectively) and increases the risk of T2DM (OR = 2.01, 95% CI = 1.04–3.10, p = 0.01). However, there was no significant difference between the three genotypes of rs7903146 and rs12255372 regarding age, BMI, glycemia, HbA1c and lipid profile. Conclusion: The present study confirmed a significant association of the TCF7L2 gene (rs7903146 (C/T) and rs12255372 (G/T) polymorphisms with a higher risk to T2DM in the Moroccan population. No significant difference in respect to anthropometric and metabolic parameters between different genotypes.

Transcription factor 7-like 2 (TCF7L2) rs12255372 variant and the risk of type 2 diabetes mellitus among the Kurdish population in Erbil, Iraq

The genetic predispositions related to type 2 diabetes (T2D) in the Middle East are poorly understood. One of the most common single-nucleotide polymorphisms (SNP) located in the transcription factor 7-like-2 (TCF7L2) gene is rs12255372 variant which elucidated a significant role in developing T2D, especially in the European population. The current study is the first to have examined the association between TCF7L2 rs12255372 variant and T2D among the Iraqi Kurdish population from Iraq. Three hundred participants were enrolled in this study: 150 were type 2 diabetic patients and 150 were normoglycemic controls. For genotyping rs12255372 (G > T) variant, Tetra ARMS-PCR was used which is high-throughput, cost and time effective technique. The genotypic frequencies in the additive genetic model (co-dominant) for GG, GT, and TT were 62.7%, 24%, and 13.3% in the normoglycemic controls, respectively, and for the diabetic patients were 50.7%, 20%, and 29.3%, respectively. The TT genotype was found considerably higher in cases when matched to the normoglycemic controls in both co-dominant and recessive models with OR (95% CI) = 2.64 (1.29–5.41) (p value = 0.006) and OR (95% CI) = 1.531 (1.232–1.902) (p value = 0.001), respectively. These frequencies indicated that the carriers of the TT genotype were more susceptible to T2D compared to other genotypes. The T allele showed a high significant frequency in T2D patients compared to the normoglycemic controls with OR (95% CI) = 1.38 (1.16–1.59) (p value = 0.000). Our results suggest rs12255372 T allele as a putative risk factor that increases the susceptibility of T2D among the Iraqi Kurdish population.

TCF7L2 rs7903146 C&gt;T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients

Abstract Objectives Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C&gt;T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C&gt;T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR). Methods The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping. Results TCF7L2 rs7903146 C&gt;T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C&gt;T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750–2.044, p=0.405). Conclusions TCF7L2 rs7903146 C&gt;T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.

TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients.

Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR). The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping. TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750-2.044, p=0.405). TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.

Association of TCF7L2 rs7903146 Polymorphism with the Risk of Type 2 Diabetes Mellitus (T2DM) Among Kurdish Population in Erbil Province, Iraq.

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.

TCF7L2 polymorphism a prominent marker among subjects with Type-2-Diabetes with a positive family history of diabetes

The greatest risk of developing type2 diabetes (T2DM) was conferred by rs7903146 SNP of Transcription factor7-like2 (TCF7L2) gene in many ethnic populations. The aim was to investigate the association of TCF7L2 (rs7903146) gene polymorphism among newly diagnosed diabetes subjects with different parental diabetes registry. A total of 171 subjects were categorized into 3 groups based on parental diabetes registry i.e. Conjugal Diabetes Registry (CDR) (n = 50), One Parental Diabetes Registry (OPDR) (n = 56) and Non Parental Diabetes Registry (NPDR) (n = 62) (control group). Kompetitive allele specific PCR (KASP) genotyping assay was used in real time PCR for identifying the genotypes. None of the biochemical parameters showed any significant difference between groups except age at onset of diabetes (p = 0.001). The T allele of TCF7L2 (rs7903146) was associated with significant risk of diabetes. TT genotype which doubles the diabetes risk showed significant association among OPDR whereas in CDR both CT and TT genotypes showed significant association than CC wild type. The ‘T’ allele of TCF7L2 SNP was associated with significant risk when compared between OPDRvsNPDR (OR 2.45, p = 0.003) and CDRvsNPDR (OR 2.82, p = 0.0007). In conclusion, TCF7L2 gene polymorphism and positive family history of diabetes are strongly associated irrespective of the presence of other risk factors among diabetes subjects.

Investigations of Associations between Seven Gene Polymorphisms and Gestational Diabetes Mellitus: Evidence From a Meta-Analysis

Background: Associations of polymorphisms in transcription factor 7 like 2 (TCF7L2), tumor necrosis factor-α (TNF-α), vitamin D receptor (VDR), and interleukin-10 with gestational diabetes mellitus (GDM) were already reported by several publications. Objectives: The aim of this meta-analysis was to better clarify associations between these polymorphisms and GDM by combing the results of all relevant publications. Methods: Eligible publications were searched from Pubmed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies. Results: Thirty-nine studies were included in this study. Combined results revealed that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms were all significantly associated with susceptibility to GDM in the total population. In subgroup analyses, we obtained similar positive findings for rs290487, rs7903146, rs1800629, and rs2228570 polymorphisms in Asians, and positive results were also observed for rs7901695, rs7903146, and rs12255372 polymorphisms in Caucasians. Conclusions: Collectively, this meta-analysis proved that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms may confer susceptibility to GDM in certain populations.

Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by the incapability of pancreas to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multifactorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β-catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis, and the incretin glucagon-like peptide 1 (GLP-1) gene. Then, TCF7L2 gene seems to affect diabetes susceptibility through B-cell dysfunction that is why we studied its association with T2DM in particular. Objectives: To investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with T2DM. Methods: A case-control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non-diabetic healthy controls age- and sex-matched with the patients. All subjects underwent full history taking; thorough clinical examination; routine laboratory investigations including hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by qRT-PCR. Results: The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68–2.6) and the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49–2.7); however, they were statistically insignificant (p value >0.05). Conclusion: Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM; however, it pointed out the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.