Transcription Factor 7-like 2 Gene Polymorphisms Research Articles

Association between Transcription Factor 7-Like 2 Gene Polymorphisms rs7903146 and rs12255372 with the Risk of Diabetic Nephropathy among South Indian Population

Abstract Introduction: Transcription factor 7-like 2 (TCF7L2) gene has been associated with the genetic predisposition of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different populations. The study aimed to explore the correlation between rs7903146 and rs12255372 polymorphisms of TCF7L2 gene and DN among the South Indian population. Methods: Polymerase chain reaction (PCR)-based direct sequencing method and allele-specific PCR were used to determine the genotypes of TCF7L2 polymorphisms in 20 normal glucose tolerance (NGT) participants, 35 T2DM patients without DN and 35 T2DM patients with DN. The differences in genotype and allelic distribution between the study groups were analyzed by Chi-square test and odds ratio (OR) with 95% confidence interval (CI) which were used to indicate the relative risk of DN. Results: The distribution of TCF7L2 gene polymorphism rs7903146 prevalence was as follows: in the NGT group, CC, 65%; CT, 30%; TT, 5%; in the T2DM without DN group, CC, 25.71%; CT, 62.86%; TT, 11.43%; and in the T2DM with DN group, CC, 31.43%; CT, 60.0%; TT, 8.57%. The distribution of rs12255372 was as follows: in the NGT group, GG, 80%; GT, 15%; TT, 5%; in the T2DM without DN group, GG, 42.86%; GT, 41.46%; TT, 8.57%; and in the T2DM with DN group, GG, 48.57%; GT, 40%; TT, 5.71%. The T allele of rs7903146 polymorphism was associated with an increased risk of T2DM without DN (OR = 3.0; 95% CI = 1.21–7.437; P = 0.010) and T2DM with DN (OR = 2.51; 95% CI = 1.00–6.252; P = 0.04), and the T allele of rs12255372 polymorphism was also associated with increased risk of T2DM without DN (OR = 3.42; 95% CI = 1.18–9.902; P = 0.018) and not with T2DM with DN when compared with NGT individuals. Conclusion: In our study, the T allele of the rs7903146 single-nucleotide polymorphism in the TCF7L2 gene confers the risk of developing DN in diabetes patients, but the T allele of the rs12255372 polymorphism in the TCF7L2 gene is associated with T2DM and its association with DN is arbitrated through T2DM.

Association of Transcription Factor 7 Like 2 (TCF7L2) ( rs7903146) Gene Polymorphisms with Some Trace Elements in the Type 2 Diabetes Mellitus Patients in Al-Najaf Governorate

The widespread prevalence of diabetes has led to a serious health risk for humans. Hyperglycemia is a hallmark of diabetes. Assessing the relation of TCF7L2 gene polymorphism (rs7903146) on the occurrence of T2DM in the Alnajaf population, and evaluating the impact of this investigated SNP on phenotypic parameters like BMI, fasting blood sugar(F.B.S), lipid profile , Mg and Zn. A case-control study of 800 individuals (400 T2DM and 400 apparently healthy control individuals) was done. The laboratory work was carried out in the laboratory of Department of Clinical Laboratory Sciences in the Faculty of Pharmacy and in the laboratory of Department of Chemistry in the Faculty of Sciences / the University of Kufa. DNA from whole blood was extracted and genotyping of TCF7L2 gene (rs7903146) polymorphism polymorphisms were carried out by RFLP –PCR. The results of this study showed that there is a significant association between the transcription factor 7-like 2 (TCF7L2) gene polymorphisms rs7903146 gene polymorphism with T2DM in the Alnajaf population. TCF7L2 gene polymorphism (rs7903146) did not show any major changes in relation to BMI, FSG, cholesterol, HDL-C, VLDL-C, or T.G, but there were significant changes in LDL, magnesium, and zinc.

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.

Lifestyle Modifications on the Expression of TCF7L2 Gene Polymorphism: A Cross-sectional Study

Introduction: Type 2 Diabetes Mellitus (T2DM) is the result of the clustering of factors along with the communication between environmental factors and a strong hereditary component. In this modern age of investigation, molecular mechanisms of Transcription Factor 7 Like 2 (TCF7L2) linking with the physiological functioning in pancreatic and intestinal endocrine cells are explored. Hitherto few studies have been done in the Indian population with regard to gene polymorphism in TCF7L2 and T2DM concerning family history. Aim: To study effect of lifestyle modifications on the expression of TCF7L2 gene polymorphism in subjects with family history of diabetes. Materials and Methods: This was a cross-sectional study, conducted over a period of 14 months September 2020 to November 2021) with 121 subjects from Shimoga district at Shimoga Institute of Medical Sciences, Shivamogga, Karnataka, India. The study was conducted after the approval by the Ethics Committee and subjects volunteering for the study have signed the informed consent. The study comprised of two groups. Both the groups had family history of T2DM, eventually persons who had not developed diabetes and had changed their lifestyle were grouped I (n=56) and subjects who had developed diabetes without any changes in their lifestyle were considered as group II (n=65). Fasting insulin, and fasting blood glucose was estimated along with the anthropometric variables like height, weight, waist circumference, hip circumference. Two Single Nucleotide Polymorphism (SNP) (rs7903146 and rs1225372) of TCF7L2 gene was genotyped using Tetra-primer Amplification Refractory Mutation System (T-ARM) protocol. Differences in clinical parameters and genotypic variants between groups, was calculated using the independent t-test and Chi-square test, a p value of <0.05 was considered statistically significant. Results: Only fasting insulin and WHR Waist Hip Ratio (WHR) parameters were weakly significant in the study population. The risk allele frequency (T) was seen to be higher in the group I and the chances of getting diabetics was 2.02 times higher than the subjects of group II for rs7903146. This substantiates that the group I subjects were more predisposed to diabetes genetically. Since subjects with heterozygous genotype (CT or GT alleles) has been associated with the highest risk of developing T2DM, the association of heterozygous genotype was high in the group with lifestyle modification and was highly significantly associated with risk of being diabetic by 7.50 times for rs7903146 and 6.10 times for rs1225372. Further risk analysis of variants according to a model of inheritance was analysed and was observed that the co-dominant and overdominant models best fitted the association with an OR above 6 for both the polymorphism. Conclusion: This study depicts that lifestyle modification masks the effect of risk variants for rs12255372 and rs7903146. The confounding nature of the influence of environmental factors over predisposition to inheritance is well depicted for the manifestation of T2DM among the genetic variants of TCF7L2.

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 >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.

TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition with various genetics and environmental influences that affects the capacity of the body to produce or use insulin resulting in hyperglycemia, whichmayleadtovariablecomplications. It is one of the world'srisinghealth problems. Thereisemerging evidence that some genetic polymorphisms can impact the risk of evolving T2DM. Wetrytodeterminetherelationship of (rs7903146) variant of the Transcription factor 7-like 2 (TCF7L2) gene with T2DM and its microvascular complications. This case-control study included 180 subjects: 60 diabetic patients without complications, 60 diabetic patients with microvascular complications and 60 matched healthy controls. Genotypes of rs7903146 (C/T) SNP in the TCF7L2 gene were evaluated by real-time polymerase chain reaction via TaqMan allelic discrimination. Logistic regression was used to detect the most independent factor for development of diabetes and diabetic microvascular complications. Variant homozygous TT and heterozygous CT genotypes were significantly increased in diabetic without complications and diabetic with complications groups than controls (p = 0.003, 0.001) respectively. The T allele was more represented in both patient groups than controls with no significant difference between patient groups. TT genotype as well as T allele was significantly associated with increased T2DM risk. The T allele of rs7903146 polymorphism of TCF7L2 confers susceptibility to development of T2DM. However, no significant association was found for diabetic complications.

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.

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.

Lack of association between single nucleotide polymorphisms in TCF7L2 and T2DM in the Chinese Yao population: A case-control study.

Single-nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 (TCF7L2) gene have been identified to be associated with the susceptibility to type 2 diabetes mellitus (T2DM) in various populations worldwide, but the results in Chinese are conflicting, and no data are available about the Liannan Yao population. Therefore, this study aimed to investigate the association of the TCF7L2 gene polymorphisms (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) with T2DM in the Yao population living in the rural areas in the Liannan Yao Autonomous County.This was a case-control study of 28 subjects with T2DM or prediabetes and 52 non-T2DM controls, all from the Chinese Yao population and recruited between January 2019 and June 2020. Patients with T2DM and prediabetes were grouped as the case group. The five SNPs (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) were examined by polymerase chain reaction and direct genomic DNA sequencing in case and control groups.The subjects in case group were older than the controls (55±14 vs 48 ± 15 years, P = .047), had higher FBG levels (9.31 ± 5.43 vs 4.09 ± 0.81, P < .001), higher TC (5.79 ± 1.29 vs 5.13 ± 1.18 mmol/L, P = .025), and higher triglycerides (2.94 ± 2.04 vs 1.86 ± 1.39 mmol/L, P = .003). The genotypic distribution for each of the SNPs was in agreement with the Hardy-Weinberg equilibrium. There were no statistically significant differences in the distributions of genotypes or alleles at all five SNPs of the TCF7L2 gene between the case and control groups (all P > .05).TCF7L2 SNPs were not associated with T2DM in the Liannan Yao population.

Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus.

BackgroundVascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM.MethodsWe conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications.ResultsThe gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2–3 and GRS 5–6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]).ConclusionThis study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.

Association of TCF7L2 gene polymorphisms, methylation, and gene-environment interaction with type 2 diabetes mellitus risk: A nested case-control study in the Rural Chinese Cohort Study.

To assess the associations of single-nucleotide polymorphisms (SNPs) and methylation of transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus (T2DM) risk and further explore the interactions among SNPs, methylation, and environmental factors involved in T2DM risk. We conducted a nested case-control study with 290 pairs of T2DM cases and matched controls. We genotyped 3 SNPs of TCF7L2 in all included participants and tested 14 CpG loci of TCF7L2 in 76 pairs of cases and controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for T2DM risk according to SNPs and methylation of TCF7L2. Multifactor dimensionality reduction (MDR) analysis was used to explore the potential TCF7L2 gene-environment interactions in T2DM risk. We found no statistically significant association between the TCF7L2 polymorphisms and T2DM risk. We observed significant positive associations of methylation at CpG5 and CpG7_8 with T2DM risk. For each 1% increase in DNA methylation at CpG5 and CpG7_8, T2DM risk increased 12% (OR 1.12, 95% CI 1.01-1.25) and 32% (OR 1.32, 95% CI 1.07-1.63), respectively. Additionally, MDR analyses identified significant SNP-environment interactions among rs290487, alcohol drinking, and hypertension and methylation-environment interactions among CpG5, CpG7_8 and hypertension (P <0.05). TCF7L2 polymorphisms were not independently associated with T2DM risk. However, TCF7L2 methylation were positively associated with T2DM risk in rural Chinese adults. Interactions among TCF7L2 polymorphisms, TCF7L2 methylation and environmental factors also suggest a possible etiologic pattern for T2DM.

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.

Transcription factor 7-like 2 gene, rs12255372 (G/T) variant and susceptibility to type 2 diabetes mellitus in North Indians

BackgroundGenetic polymorphisms of the Transcription Factor 7-Like 2 (TCF7L2) gene have been shown to be strongly associated with susceptibility to type 2 diabetes mellitus (T2DM) and its related complications across several ethnicities. ObjectivesThe aim of the present study was to investigate the association of rs12255372 (G/T) polymorphism in TCF7L2 gene with the risk of T2DM in the Indian population. MethodsWe included a total of 712 human subjects (327 T2DM subjects and 385 healthy controls) for various anthropometric, biochemical and genetic parameters. Genotyping of TCF7L2 gene was carried out using the PCR-RFLP method. ResultsSignificantly higher values of body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), and body fat (%) were observed in T2DM subjects than controls (p ≤.001). Dyslipidemia represented by higher levels of triglycerides and reduced values of high-density lipoprotein (HDL) was more predominant in T2DM subjects compared to healthy controls. Both microvascular and macrovascular complications were predominant in T2DM patients than controls. The risk genotype (TT) frequency of TCF7L2 gene was significantly higher in T2DM subjects compared to controls (19.4% vs. 9.8%). The “T” allele was more predominant in T2DM subjects than healthy controls. Logistic regression analysis of the data indicates that the TT genotype of TCF7L2 gene is associated with appox. 2-fold increased risk of developing T2DM (OR = 1.91 95% CI (1.16–3.16); p = .014). Interestingly, no significant association among the genotypic distribution of metabolic traits in T2DM and healthy subjects. ConclusionThe present study established a significant association of TCF7L2 gene (rs12255372 (G/T) polymorphism) with a higher risk of T2DM in the North Indian population.

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.

A possible association between rs7903146 (C/T) polymorphism of the transcription factor 7-like 2 gene and type 2 diabetes mellitus in Egyptians

Background Type 2 diabetes mellitus (T2DM) is a very common polygenic metabolic disorder. Single-nucleotide polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been reported to affect T2DM susceptibility by affecting insulin secretion and via its involvement in the Wnt signaling pathway. Patients and methods The present study investigated the association of rs7903146(C/T) polymorphism of the TCF7L2 gene with T2DM. The study involved 42 Egyptian adults who were diagnosed with T2DM and 42 healthy adults taken as controls. Allele-specific PCR was performed to detect TCF7L2 gene polymorphism. Results No association was found between the rs7903146 polymorphisms of TCF7L2 gene and susceptibility to T2DM, using both dominant and recessive models. Conclusion In our study, we could not prove the suggested association between rs7903146(C/T) polymorphism of the TCF7L2 gene and T2DM in Egyptians. Further Egyptian studies are needed to confirm the results of this study.

The correlation between polymorphism of TCF7L2 gene and the incidence of type 2 Diabetes in Asian: a meta analysis

Transcription Factor7-like2 (TCF7L2) geneplays a role in the control of proglucagon production which is the precursor of the glucagon-like peptide-1 (GLP-1) hormone. GLP-1 protein plays a role in the homeostasis of blood sugar levels by increasing insulin secretion. The presence of this gene variant in beta cells of the pancreas shows impaired insulin secretion in in vivo and in vitro studies.The objective of this study was to strengthen some research results related to the role of TCF7L2 gene polymorphisms in lowering insulin secretion and its correlation to the incidence of type 2 diabetes mellitus (T2DM) through an analysis. This study is a quantitative study based on a literature study (meta-analysis).The framework of the meta-analysis concept was based on the determination of odds ratio (OR), standard error (SE), determination of 95% Confidence Interval from ln (OR) and 95% for OR.Furthermore, the calculation of meta-analysis was performed. The analysis was conducted on 27 research results about TCF7L2 gene polymorphism which have been disclosed by 87 researchers in various research. Based on the results of data analysis, the correlation value was 2.6 and was in the acceptance of 95% confidence interval. Genetic and functional data indicate that the TCF7L2 gene plays an important role in insulin secretion and the intermediate phenotypes are associated with adipocytes.The TCF7L2 gene can activate special proteins that affect insulin secretion and sensitivity. The TCF7L2 protein is a transcription factor that regulates the proglucagon gene. Proglucagon is a precursor of the Glucagon-like peptide-1 (GLP-1) hormone, an insulinotropic hormone produced by enteroendocrine cells. TCF7L2 gene polymorphism plays an important role to decrease the secretion of GLP-1 and ultimately leads to decreased insulin secretion.Based on the correlation value, it can be concluded that there is a relationship between TCF7L2 gene polymorphism and the incidence of T2DM.

Association of variants of the TCF7L2 gene at rs7903146(C/T) and rs12255372(G/T) with type 2 diabetes mellitus in Chennai suburban population

Association of variants of the TCF7L2 gene at rs7903146(C/T) and rs12255372(G/T) with type 2 diabetes mellitus in Chennai suburban population - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.043, International Journal of Clinical Biochemistry and Research-Int J Clin

Role of TCF7L2 and PPARG2 Gene Polymorphisms in Renal and Cardiovascular Complications among Patients with Type 2 Diabetes: A Cohort Study

Background: The emerging renal and cardiovascular complications of type 2 diabetes (T2DM) genetics involves differently assembled gene variants including transcription factor 7-like 2 (TCF7L2) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) polymorphisms. However, the relevance of these genes for complication prediction has not been extensively tested. Methods: We analyzed the SNP rs7903146 variants in TCF7L2 and PPARG2 gene polymorphisms for their contribution to the incidence of chronic kidney disease (CKD) and cardiovascular complications in a prospective cohort study. All T2DM patients were followed up to estimate the glomerular filtration rate and cardiovascular outcomes. Cox proportional hazards regression models were used to estimate the genotype effect on the incidence of CKD and vascular complications. Results: A total of 422 patients were included. SNP rs7903146 variants in the TCF7L2 gene were classified into 3 groups: CC, 385 patients (91.2%), CT, 32 patients (7.6%), and TT, 5 patients (1.2%), while in the PPARG2 gene they were classified into 2 groups: Pro12Pro, 404 patients (95.7%) and Pro12Ala, 18 patients (4.3%). The prevalence of CKD, cardiovascular disease, and death at the end of the 5-year follow-up was 16.8, 29, and 7.9%, respectively. The Pro12Ala variant of the PPARG2 gene was significantly associated with increased CKD risk at the end of the study (adjusted HR 3.45, 95% CI 1.01–11.77, p = 0.046); it showed a significant association with increased cerebrovascular risk, but not cardiovascular disease and mortality. No genotype effect of rs7903146 in the TCF7L2 gene was apparent on renal and cardiovascular complications, except the TT variant of rs7903146 increased cardiovascular events when compared with the non-TT variant. Conclusion: The findings of our study were that the Pro12Ala variant in the PPARG2 gene was associated with risk of developing CKD and cerebrovascular disease in Asian T2DM subjects in a prospective cohort study. The TCF7L2 polymorphism was not associated with cardiovascular outcomes.

Associations of TCF7L2 gene polymorphisms with the risk of diabetic nephropathy: A case-control study.

The aim of the study was to explore the correlation between rs7903146 and rs290487 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene and diabetic nephropathy (DN) in Chinese Han population.Polymerase chain reaction–restriction fragment length polymorphism was used to determine genotypes of TCF7L2 polymorphisms in 90 patients with DN and 96 diabetes patients without DN. The linkage disequilibrium (LD) and haplotype analysis were performed with haploview software. Hardy–Weinberg equilibrium was assessed in the control group based on the genotype distributions of TCF7L2 polymorphisms. The genotype, allele, and haplotype distribution differences between the case and control groups were analyzed by chi-squared test, and odds ratio (OR) and 95% confidence interval (CI) were used to indicate the relative risk of DN.People carrying TT genotype of rs7903146 were more easily to be attacked by DN than CC genotype carriers (P = .02, OR = 4.26, 95% CI = 1.12–16.24). Meanwhile, T allele also showed 1.85 times risk to suffer from DN compared with C allele (OR = 1.85, 95% CI = 1.02–3.10). However, there was no significant difference in genotypes and alleles frequencies of rs290487 between 2 groups. The strong LD existed between the 2 single nucleotide polymorphisms and haplotype T–T (rs7903146–rs290487) increased the susceptibility to DN (OR = 2.63, 95% CI = 1.31–5.25).TCF7L2 rs7903146 polymorphism may be associated with the susceptibility to DN in Chinese Han population, but rs290487 is not. Additionally, haplotype is also a risk factor for DN.

Genetic polymorphisms of human transcription factor-7 like 2 (TCF7L2), β-defensin (DEFB1) and CD14 genes in nephrolithiasis patients

BackgroundIt is assumed that genetic factors play crucial role in nephrolithiasis. The present study was conducted to explore the role of Human Transcription Factor-7 like-2 (TCF7L2) β-defensin (DEFB1) and CD14 gene polymorphism in development and progression of nephrolithiasis. MethodsThe genotypes of TCF7L2, DEFB1 and CD14 polymorphism were determined in 240 nephrolithiasis patients and 240 healthy controls by restriction digestion method of PCR. The levels of serum TCF7L2, DEFB1, CD14, uric acid and other biochemical parameters were measured both in nephrolithiasis patients and healthy control. ResultsThe patients and control groups showed 30% and 50% 1654 AA DEFB1 genotype respectively. The Allele frequency in case of patient's group was 63.67% while in control group it was 36.33%. The mean serum DEFB1 levels of the patients and control groups attained were 115.66 and 239.43 pg/mL respectively. The allele frequency of TCF7L2 in patients and controls were 44.17% and 70.0% for C-allele, 55.83% and 30.00% for T-allele respectively. The mean of serum TCF7L2 levels were significantly decreased in patients compared to control group. ConclusionsThe present findings are first of its class that validates a considerable connection of DEFB1 and TCF7L2 gene polymorphisms with nephrolithiasis and could probably act as indicators to estimate the risk associated to nephrolithiasis.