Transcription Factor 7-like 2 Polymorphisms Research Articles

Effect of the variant rs7903146 of Transcription factor 7-like 2(TCF7L2) gene on anthropometric and metabolic responses to a 24 weeks meal replacement Hypocaloric diet.

Some studies have demonstrated the effect of the rs7903146 genetic variant on weight response after different dietary strategies. The objective of our study was to evaluate the role of this genetic variant of the TCF7L2 gene on weight loss and diabetes mellitus progression following a partial meal replacement (pMR) hypocaloric diet. We conducted an interventional study in 214 subjects with obesity and a body mass index (BMI) > 35 kg/m². The subjects received two servings per day of a normocaloric hyperproteic formula for 24 weeks as part of a pMR diet. Body weight, body mass index (BMI), fat mass, waist circumference, lipid profile, fasting insulin levels, and HOMA-IR were determined. All patients were genotyped for rs7903146 and evaluated under a dominant model (CC vs. CT+TT). The decrease at 24 weeks was higher in non-T allele carriers compared to T allele carriers (BMI: -3.3±0.3 kg/m² vs. -2.2±0.2 kg/m², p=0.02; weight: -9.5±1.1 kg vs. -5.0±1.0 kg, p=0.01; fat mass: -8.7±0.2 kg vs. -4.0±0.2 kg, p=0.04; waist circumference: -8.0±0.2 cm vs. -3.0±0.4 cm, p=0.04; glucose levels: -7.1±1.2 mg/dL vs. -1.2±1.1 mg/dL, p=0.01; insulin: -10.1±1.1 µIU/L vs. -4.0±1.0 µIU/L, p=0.01; HOMA-IR: -2.1±1.1 units vs. -0.5±0.1 units, p=0.01; C-reactive protein: -0.9±0.1 mg/dL vs. -0.4±0.2 mg/dL, p=0.01; triglycerides: -17.1±0.1 mg/dL vs. -9.1±0.2 mg/dL, p=0.01; and HbA1c: -1±0.1% vs. -0.3±0.2%, p=0.01). Following the dietary intervention, only non-T allele carriers showed a significant decrease in the frequency of hypertriglyceridemia, abdominal waist, hyperglycemia, and DM2. The TCF7L2 (rs7903146) polymorphism modulates pMR diet-induced changes in body weight, lipid metabolism, and insulin resistance. These changes lead to a significant decrease in the prevalence of hyperglycemia and other components of metabolic syndrome.

Diabetes Risk Allele of Transcription Factor 7-like 2 (TCF7L2) Polymorphisms is Associated with Higher Glucagon-like Peptide 1 (GLP1) and Lower Insulin Secretion

BACKGROUND: The most influential susceptible gene associated with diabetes, transcription factor 7-like 2 (TCF7L2), has been observed in diverse populations. TCF7L2 influences type 2 diabetes risk through glucagon-like peptide 1 (GLP1) production. The presence of risk allele of TCF7L2 leads to the alteration of gene expression in pancreatic beta cells; however, how the mechanism is related with GLP1 remains unclear. This study was conducted to explore the variations of GLP1 increment and insulin secretion between individuals with and without diabetes risk allele of single nucleotide polymorphisms (SNPs) in TCF7L2.METHODS: A cross-sectional analytic study was conducted involving individuals subjects who harbored known variants of SNPs in the TCF7L2: heterozygote or mutant of rs12255372 (GT or TT), rs7903146 (CT or TT), rs10885406 (AG or GG); as well as control subjects with wild type of rs12255372 (GG), rs7903146 (CC), and rs10885406 (AA). Anthropometric parameters, blood glucose, insulin, and GLP1 were measured; and homeostasis model assessment-beta cell (HOMA-%B) index was calculated.RESULTS: The GLP1 increment response was higher in subjects carrying the diabetes risk allele (0.34±0.80 ng/mL) than those with the wild type (-0.04±0.57 ng/mL) (p=0.041). The HOMA-%B was reduced in subjects carrying the diabetes risk allele (71.64±24.72) than those with the wild type (103.23±68.00) (p=0.011). Among individuals carrying the diabetes risk allele, the likelihood of GLP1 increment with high response was twice as high (p=0.007), while the occurrence of low HOMA-%B was 1.47 more frequent (p=0.011).CONCLUSION: TCF7L2 polymorphisms were associated with the GLP1 increment response and reduced HOMA-%B, which might be potentially contributing to GLP1 resistance in patients with diabetes risk factors.KEYWORDS: diabetes risk, TCF7L2, GLP1, HOMA-%B

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 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 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.

Transcription factor 7-like 2 single nucleotide polymorphisms rs290487 and rs290481 are associated with dyslipidemia in the Balinese population.

BackgroundDyslipidemia is one of the major risks for the development of cardiovascular diseases which has been the leading cause of death in developing countries. Previously, common polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with altered lipid profiles. In this study, we investigated the associations of TCF7L2 SNPs, rs290487 and rs290481, with dyslipidemia and altered lipid profile in the Balinese.MethodsA total of 565 subjects from four locations in the Bali Province, Indonesia, were recruited. Serum lipid concentrations (triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)) were measured using standard protocol. SNP genotyping was done using the amplification refractory system mutation polymerase chain reaction (ARMS-PCR) method.ResultsWe found the shifted major/minor allele frequencies of both SNPs (0.56 for rs290487 T allele, 0.53 for rs290481 T allele) in the Balinese, as compared to dbSNP. The rs290487 and rs290481 C alleles were significantly associated with dyslipidemia, particularly high TC and high LDL-C. These associations were independent of age, sex, population, obesity, diabetes mellitus, and high TyG index as a proxy for insulin resistance. The haplotype CC also showed similar association with these traits. Our findings indicate that TCF7L2 polymorphisms are associated with dyslipidemia and altered lipid profile in the Balinese.

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. 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. 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. 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.

Transcription factor 7-like 2 (TCF7L2): a culprit gene in Type 2 Diabetes Mellitus

The genetics of Type 2 diabetes a complex metabolic disorder, characterized by decreased insulin secretion and insulin resistance resulting in impaired blood glucose homeostasis remains enigma for geneticists. In 2006 an important step while finding genetic causes of diabetes type 2 was identification of transcription factor 7-like 2 (TCF7L2) gene an important marker in predisposition of type 2 diabetes in almost all ethnic population. Recent genetic research identifies numerous novel type 2 diabetes susceptible genes among these genes TCF7L2 is considered as gang head and emerged as the most promising types 2 diabetes causing gene. Risk variants in TCF7L2 effects pancreatic beta cell development and insulin secretion by influencing Wnt Signaling pathway. Genetic variants in TCF7L2 confer risk for type 2 diabetes by altering expression of transcription factor (which has key role in blood glucose regulation) in pancreas. The purpose of this paper is to evaluate type 2 diabetes susceptible gene the TCF7L2 and to present a comprehensive review of studies carried out worldwide in different ethnic population on association of TCF7L2 polymorphism with type 2 diabetes.

Фактор транскрипции 7 (TCF7L2): фактор риска развития сахарного диабета 2 типа

The genetics of Type 2 diabetes a complex metabolic disorder, characterized by decreased insulin secretion and insulin resistance resulting in impaired blood glucose homeostasis remains enigma for geneticists. In 2006 an important step while finding genetic causes of diabetes type 2 was identification of transcription factor 7-like 2 (TCF7L2) gene an important marker in predisposition of type 2 diabetes in almost all ethnic population. Recent genetic research identifies numerous novel type 2 diabetes susceptible genes among these genes TCF7L2 is considered as gang head and emerged as the most promising types 2 diabetes causing gene. Risk variants in TCF7L2 effects pancreatic beta cell development and insulin secretion by influencing Wnt Signaling pathway. Genetic variants in TCF7L2 confer risk for type 2 diabetes by altering expression of transcription factor (which has key role in blood glucose regulation) in pancreas. The purpose of this paper is to evaluate type 2 diabetes susceptible gene the TCF7L2 and to present a comprehensive review of studies carried out worldwide in different ethnic population on association of TCF7L2 polymorphism with type 2 diabetes.

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.

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.

TCF7L2 polymorphisms are associated with amygdalar volume in elderly individuals with Type 2 Diabetes

The association between several Single Nucleotide Polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene and Type 2 Diabetes (T2D) as well as additional T2D-related traits is well established. Since alteration in total and regional brain volumes are consistent findings among T2D individuals, we studied the association of four T2D susceptibility SNPS within TCF7L2 (rs7901695, rs7903146, rs11196205, and rs12255372) with volumes of white matter hyperintensities (WMH), gray matter, and regional volumes of amygdala and hippocampus obtained from structural MRI among 191 T2D elderly Jewish individuals. Under recessive genetic model (controlling for age, sex and intracranial volume), we found that for all four SNPs, carriers of two copies of the T2D risk allele (homozygous genotype) had significantly smaller amygdalar volume: rs7901695- CC genotype vs. CT + TT genotypes, p = 0.002; rs7903146-TT vs. TC + CC, p = 0.003; rs11196205- CC vs. CG + GG, p = 0.0003; and rs12255372- TT vs. TG + GG, p = 0.003. Adjusting also for T2D-related covariates, body mass index (BMI), and ancestry did not change the results substantively (rs7901695, p = 0.003; rs7903146, p = 0.005; rs11196205, p = 0.001; and rs12255372, p = 0.005). Conditional analysis demonstrated that only rs11196205 was independently associated with amygdalar volume at a significant level. Separate analysis of left and right amygdala revealed stronger results for left amygdalar volume. Taken together, we report association of TCF7L2 SNPs with amygdalar volume among T2D elderly Jewish patients. Further studies in other populations are required to support these findings and reach more definitive conclusions.

Incidence and association of TCF7, TCF7L2 single nucleotide polymorphisms in type 1 diabetes mellitus patients of South Tamil Nadu, India

Background: The TCF family genes TCF7 (T cell specific transcription factor-7) and TCF7L2 (transcription factor 7 like 2) are increasingly recognized to play a pivotal role in the incidence, pathophysiology of type 1 diabetes mellitus (T1DM). However, the prevalence and the influence of these allelic variants in the Indian/south Indian T1DM population is completely obscure.Methods: Genomic DNA was isolated from the peripheral blood samples of healthy controls, T1DM patients, and PCR (polymerase chain reaction), restriction fragment length polymorphism (RFLP), allele specific PCR (ASP), PCR product sequencing strategies were utilized to determine the prevalence of the TCF7 (exon 3, flanking intron 2, 3 regions) and TCF7L2 (intron 4) polymorphisms. Clinical investigations included assessment of the blood glucose/ estimated average glucose levels (EAG) and C-peptide levels.Results: The results indicate that 34.9% and 3.17% of the T1DM patients harbored the TCF7L2 rs7903146 and the TCF7 rs386692598 polymorphisms, respectively. Assessment of biochemical parameters indicated that the rs7903146 positive T1DM patients exhibited significantly lower EAG levels (p&lt;0.05), suggesting that these patients may exhibit phenotypic heterogeneity, a milder disease course. The study further demonstrates that PCR based strategies enable reliable molecular diagnosis of T1DM in small scale diagnostic units.Conclusions: T1DM patients from south Tamil Nadu present TCF7, TCF7L2 genetic variations and screening for these polymorphisms will empower physicians to provide appropriate therapy and genetic counselling.

Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146

The transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146 is known to be tightly associated with an elevated risk for type 2 diabetes, whereas the molecular mechanisms remain elusive. We evaluated the metabolic profile of a total of 394 patients’ serum samples with respect to their rs7903146 genotype using targeted metabolomics in a discovery (n = 154) and a validation (n = 240) study. We have identified serotonin as the top metabolite being increased in carriers of the risk allele. Serotonin was significantly associated with the rs7903146 genotype after full adjustment including type 2 diabetes and further top ranked metabolites. Given the role of peripheral serotonin in metabolic homeostasis and type 2 diabetes, this finding provides a first hint that the well-known impact of the TCF7L2 polymorphism on type 2 diabetes risk may involve a serotonin-dependent pathway.

A meta-analysis on genetic associations between Transcription Factor 7 Like 2 polymorphisms and type 2 diabetes mellitus

BackgroundSome previous studies already explored associations of Transcription Factor 7 Like 2 (TCF7L2) polymorphisms with type 2 diabetes mellitus (T2DM), with conflicting findings. Here, we aimed to better analyze the relationship between TCF7L2 polymorphisms and T2DM in a larger combined population by performing a meta-analysis. MethodsWe searched Pubmed, Embase, Web of Science and CNKI for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between TCF7L2 polymorphisms and T2DM. ResultsTotally 42 studies were included for this meta-analysis. The meta-analysis results demonstrated that TCF7L2 rs4506565, rs7901695, rs11196205 and rs12255372 polymorphisms were all significantly associated with susceptibility to T2DM in general population. Further subgroup analyses revealed similar significant findings in both Asians and Caucasians. ConclusionsOur findings supported that these TCF7L2 polymorphisms could be used to identify individuals at high risk of developing T2DM.

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.