Transcription Factor 7-like 2 Gene Research Articles

Association of rs7903146 polymorphism in the TCF7L2 gene with diabetic nephropathy and decreased estimated GFR in an Arab population in southwest Iran

Background: Transcription factor 7-like 2 (TCF7L2) acts as a downstream effector in the Wnt signaling pathway. It plays important roles in the proliferation and differentiation of islet betacell, insulin secretion and kidney development. Objectives: This study aimed to demonstrate whether rs7903146 variant is associated with diabetic nephropathy (DN) and measures of kidney function in a diabetic and healthy Arab population in southwest of Iran. Patients and Methods: This study is comprised of 132 diabetic subjects (T2DM) and 66 healthy participants. The diabetic subgroups were composed of patients with DN (n=56) and early onset of diabetes (n=71). The rs7903146 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in all the participants. Blood glucose, HbA1c, blood urea nitrogen (BUN), creatinine and urinary albumin were evaluated by a biochemistry analyzer and enzyme-linked immunosorbent assay (ELISA) was employed for cystatin C measurement. Results: The frequency of genotypes was significantly different between all the diabetic cases and control subjects (P<0.05). The TT variant odds ratio (OR) versus CT/CC genotypes for diabetes was 2.47 (95% CI 1.11-5.48). An association was observed between TT homozygous and DN (OR for TT 2.78, 1.13-6.84). Early onset diabetic patients showed stronger association (OR: 4.64, 1.64-13.14, P=0.003). The TT genotype was also found to be a risk variant for decreased estimated glomerular filtration rate (eGFR)(Cys-Cr) below 60 mL/min/1.73 m2 (OR: 3.36, 1.4-8.1, P=0.005). Conclusions: The results confirmed that the TCF7L2 gene rs7903146 variants are significantly associated with T2DM in Arab population of Iran. The TT genotype of this SNP is also predisposed to the risk of developing DN especially in subjects with early onset diabetes. Patients with TT genotype were also at risk of decreased GFR.

TCF7L2 gene variants predispose to the development of type 2 diabetes mellitus among individuals with metabolic syndrome.

Transcription factor 7-like 2 (TCF7L2) gene variants rs12255372 and rs7903146 have been consistently shown to raise genetic risk for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the possible role of these variants in the development of impaired glucose metabolism (IGM), including impaired fasting glucose (IFG) or T2DM, in patients with metabolic syndrome (MS). The study population consisted of 228 patients with MS who were divided into two groups. The first group consisted of 148 patients with MS and IGM [39M/109F, 59.8 ± 14.6 (mean ± SD) years] and the second group of 80 patients with MS and normoglycemia (NGM) (16M/64F, 56.1 ± 15.8years). The diagnosis of MS was based on the criteria proposed by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Anthropometric parameters including BMI and waist circumference were recorded and blood samples were obtained after overnight fasting for biochemical tests. The rs12255372 and rs7903146 TCF7L2 polymorphisms were genotyped in peripheral blood leucocytes. Analysis of the distribution of the TCF7L2 polymorphic alleles revealed that the frequency of the T allele of the TCF7L2 variant rs12255372 was 38.2% in the study population, while the frequency of the T allele of the TCF7L2 rs7903146 variant was 35.3%. The T allele of the rs12255372 variant was more frequently present in patients with MS and IGM (48.3%) compared to patients with MS and NGM (19.4%, p < 0.001). Also, the T allele of rs7903146 was more frequently present in patients with MS and IGM (44.6%) compared to patients with MS and NGM (18.1%, p < 0.001). Logistic regression analysis followed and revealed that the presence of the T allele for both rs12255372 and rs7903146 TCF7L2 gene variants is a very powerful predictor of the presence of glucose disorders, increasing the risk more than fourfold in patients with MS and after adjustment for potential confounders, such as age, gender, BMI, and waist circumference (TCF7L2 rs12255372: Exp(B) 4.917, p < 0.001 and TCF7L2 rs7903146: Exp(B) 5.460, p < 0.001). The presence of the rs12255372 and rs7903146 TCF7L2 gene variants plays an important role in the development of T2DM among individuals with MS. These findings support the notion that among subjects with MS, those who finally develop T2DM have a genetic predisposition to β-cell dysfunction.

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.

Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

Transcription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk allele of the rs7903146 in the TCF7L2 gene increases the risk of type 2 diabetes based on real-time stable isotope measurements of insulin synthesis during an Oral Glucose Tolerance Test. In addition, we performed oral minimal model (OMM) analyses to assess insulin sensitivity and β cell function indices. Compared to unaffected relatives, individuals with type 2 diabetes had lower OMM indices and a higher level of insulin synthesis. We found a T allele-dosage effect on insulin synthesis and on glucose tolerance status, therefore insulin synthesis was higher among T-allele carriers with type 2 diabetes than in wild-type individuals. These results suggest that hyperinsulinemia is not only an adaptation to insulin resistance, but also a direct cause of type 2 diabetes.

Methylation of Tcf712 promoter by high-fat diet impairs β-cell function in mouse pancreatic islets.

The TCF7L2 (transcription factor 7 like 2) gene is strongly associated with type 2 diabetes risk. However, many people without the TCF7L2 at-risk allele develop T2D. The aim of this study was to investigate altered Tcf7l2 DNA methylation and gene expression caused by high-fat diets (HFDs). C57BL/6 mice were fed either an HFD or normal diet for 8weeks, and intraperitoneal glucose tolerance tests were performed. Pancreatic islets were sorted for bisulfite sequencing polymerase chain reaction to determine DNA methylation status. We cloned the Tcf7l2 promoter, methylated it with methyltransferase, and transfected this construct into MIN-6 cells to confirm the effects of promoter methylation on Tcf7l2 expression. Aberrant methylation at position -165bp relative to the transcriptional start site of Tcf7l2 was present in mice fed an HFD. Accordingly, expression of Tcf7l2 mRNA and its corresponding protein was lower in the HFD group (P<.05). Methylation of the Tcf7l2 promoter suppressed gene expression in MIN-6 cells. An HFD was shown to induce aberrant methylation of the Tcf7l2 promoter in mouse islets, which resulted in diminished gene expression. This study provides an evidence of the association between nutrient consumption and gene expression.

The role of genetic variation in TCF7L2 and KCNJ11, dietary intake, and physical activity on fasting plasma glucagon-like peptide-1 in male adolescents

Background Transcription factor 7-like 2 (TCF7L2) and potassium voltage-gated channel subfamily j member 11 (KCNJ11) gene polymorphisms have been associated with type 2 diabetes mellitus (T2DM) via regulation of insulin production. Ingested nutrients induce glucagon-like peptide-1 (GLP-1), which in turn induces insulin secretion.Objective To evaluate the relationship between TCF7L2 and KCNJ11 gene polymorphism, dietary intake, and physical activity on fasting plasma GLP-1 in normal male adolescents.Methods This observational study with a cross-sectional design included 54 male adolescents selected from high schools in Yogyakarta, Indonesia. Interviews were done to collect data on energy intake and physical activity. The GLP-1 and insulin levels were measured from fasting blood plasma. The TCF7L2 and KCNJ11 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results Fasting GLP-1 was positively correlated with energy intake (r=0.276; P=0.047), but not with physical activity (r=0.011; P=0.936). The GLP-1 concentration was not associated with TCF7L2 and KCNJ11 gene polymorphisms (all P&gt;0.05). In subjects with an EE genotype (KCNJ11), GLP-1 was not correlated with insulin (r=-0.036; P=0.435). However, in subjects with an EK genotype (KCNJ11), GLP-1 was positively correlated with insulin (r=0.394; P=0.026).Conclusion GLP-1 concentration is positively correlated with body weight. Among male adolescents with a genetic variation in KCNJ11 (EK genotype), there is a significant correlation between GLP-1 and insulin signalling.

The role of genetic variation in TCF7L2 and KCNJ11, dietary intake, and physical activity on fasting plasma glucagon-like peptide-1 in male adolescents

Background Transcription factor 7-like 2 (TCF7L2) and potassium voltage-gated channel subfamily j member 11 (KCNJ11) gene polymorphisms have been associated with type 2 diabetes mellitus (T2DM) via regulation of insulin production. Ingested nutrients induce glucagon-like peptide-1 (GLP-1), which in turn induces insulin secretion.Objective To evaluate the relationship between TCF7L2 and KCNJ11 gene polymorphism, dietary intake, and physical activity on fasting plasma GLP-1 in normal male adolescents.Methods This observational study with a cross-sectional design included 54 male adolescents selected from high schools in Yogyakarta, Indonesia. Interviews were done to collect data on energy intake and physical activity. The GLP-1 and insulin levels were measured from fasting blood plasma. The TCF7L2 and KCNJ11 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results Fasting GLP-1 was positively correlated with energy intake (r=0.276; P=0.047), but not with physical activity (r=0.011; P=0.936). The GLP-1 concentration was not associated with TCF7L2 and KCNJ11 gene polymorphisms (all P&gt;0.05). In subjects with an EE genotype (KCNJ11), GLP-1 was not correlated with insulin (r=-0.036; P=0.435). However, in subjects with an EK genotype (KCNJ11), GLP-1 was positively correlated with insulin (r=0.394; P=0.026).Conclusion GLP-1 concentration is positively correlated with body weight. Among male adolescents with a genetic variation in KCNJ11 (EK genotype), there is a significant correlation between GLP-1 and insulin signalling.

Screening of Polymorphisms of Transcription Factor 7-like 2 Gene in Polycystic Ovary Syndrome using Polymerase Chain Reaction-restriction Fragment Length Polymorphism Analysis.

Background:Polycystic ovary syndrome (PCOS) is a common endocrine disorder occurring in premenopausal women, with a prevalence rate of 5%–7%. It has been observed in multiple number of studies the coexistence between diabetes mellitus 2 and obesity with this endocrinopathic disorder. Transcription factor 7-like 2 (TCF7L2) gene is shown to be associated with insulin secretion.Aim:To screen whether the gene variant of TCF7L2 (formerly TCF4) gene is significantly associated and has susceptibilities with type 2 diabetes in PCOS. This study is essential to uncover diabetogenic association of the TCF7L2 gene variants with PCOS.Design:This was a hospital-based study.Methods:In this work, blood samples from 43 PCOS patients with age and sex similar to 43 control samples were collected, followed by isolation of DNA. Further genotyping of the TCF7L2 gene was carried out by performing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Statistical Analysis:Genotype frequencies of the TCF7L2 rs7903146 gene were checked by Hardy–Weinberg equilibrium of genotype in both PCOS and the control group, and also, the frequencies of the genotype were performed accordingly.Results:There was no significant allelic variation observed among the patient and the control samples. From the patient details, it was observed that women between the age group of 21 and 25 years are susceptible to PCOS.Conclusion:From the PCR-RFLP analysis, it can be stated that there are no expected gene polymorphisms seen in this study, unlike the study carried out on the Chinese population where they observed genotype variations CC, CT, and TT. From this study, we can conclude that TCF7L2 rs7903146 gene cannot be considered as the candidate gene for the occurrence of PCOS.

Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol.

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the ‘T’ allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions between the SNPs and lifestyle factors were statistically significant after correction for multiple testing. Our findings indicate that the association between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in this Asian Indian population.

TCF7L2 gene polymorphisms rs12255372, rs7903146, rs10885406 and the association with type 2 diabetes in a population of Legian Village, Kuta, Bali.

Background: Polymorphisms in the transcription factor 7 like-2 (TCF7L2) gene have been consistently reported to be associated with increased risk of type 2 diabetes mellitus in various populations, in particular, the rs7903146, rs12255372, and rs10885406 polymorphism. Objective: The aim of this study was to investigate whether these polymorphisms in the Balinese population of Legian village. Methods: A cross-sectional study enrolling 286 participants (178 male, 108 female), mean age was 46.0±10.0 (range 20–83) years. PCR-RFLP conducted genotyping for rs7903146, rs12255372, and rs10885406 polymorphism, fasting and two hours after meal blood glucose were measured. Student’s t-test and analysis of variance (ANOVA) and chi-square test were employed.  Results: The frequencies of the CC and CT genotypes of the rs7903146 polymorphism were 93.4% and 6.6%. The GG and GT genotypes of the rs12255372 polymorphism were 94.8% and 5.2%, while in the rs10885406 they were 87.1%, 12.2%, and 0.7% for the AA, AG, and GG genotypes. The TT genotypes of the rs7903146 and rs12255372 not found. The prevalence of type 2 diabetes in this population were 9.0%. The frequency of the CT genotype of the rs7903146 was higher in diabetes compare to the non-diabetes group (7.6% vs. 6.5%, p=0.822), while GT genotype in rs12255372 was lower (3.8% vs. 5.3%, p=0.737). The AG genotype of the rs10885406 also lower in diabetes group (7.6% vs. 12.6%, p=0.679). In the CT genotype of rs7903146, the two hours after meal blood glucose were significantly higher (141.15 ± 125.06 vs. 107.50 ± 46.94, p=0.012). Interestingly, although not statistically significant, individuals with the GG genotype showed the lowest blood glucose. Conclusion: Rs7903146, rs12255372, and rs10885406 polymorphisms in the TCF7L2 genes did not show association with type 2 diabetes in the Balinese population of Legian Village. However, two hours after meal blood glucose level was found to be significantly higher in the CT genotype of the rs7903146.

Type 2 diabetes mellitus and TCF7L2 gene rs12255372 G/T polymorphism: a meta-analysis involving 7990 subjects

The transcription factor 7-like 2 (TCF7L2) G/T gene polymorphism, also known as rs12255372, has been linked to increases in risk for type 2 diabetes (T2DM), especially in the European population. However, a clear consensus on the subject is still lacking in analyses of the Chinese population. To explore the relationship between the TCF7L2 gene polymorphism and T2DM in the Chinese population, we conducted a meta-analysis of 7990 subjects from ten studies. Depending on whether heterogeneity was present, we employed either a fixed or random-effects model, respectively, to assess the pooled odds ratio (ORs) and their corresponding 95% confidence interval (95% CI). TCF7L2 rs12255372 G/T gene polymorphism was significantly associated with T2DM in the Chinese population under allelic (OR 1.38, 95% CI 1.20–1.60, p = 8.59 × 10−6), dominant (OR 1.67, 95% CI 1.20–2.32, p = 0.002), heterozygous (OR 1.65, 95% CI 1.18–2.31, p = 0.003), and additive genetic models (OR 1.53, 95% CI 1.13–2.07, p = 0.006). In the Chinese population, TCF7L2 rs12255372 G/T gene polymorphism may correlate with an increased risk of T2DM. T allele of TCF7L2 rs12255372 G/T gene polymorphism might confer a genetic risk for T2DM in the Chinese population.

Tcf7l2 Gene Polymorphism in T2dm with Patients in Turkish Population

Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects of insulin secretion and/or increased cellular resistance to insulin. Chronic hyperglycemia and other metabolic disturbances of DM lead to long-term tissue and organ damage as well as dysfunction involving the eyes, kidneys, and nervous and vascular systems. Type 2 Diabetes mellitus; is the most common form of DM worldwide, and its prevalence is increasing. Its underlying defects can vary from predominant insulin resistance with relative insulin deficiency to a predominant insulin secretory defect with insulin resistance. Transcription 7-like 2 (TCF7L2) protein has been implicated in blood glucose homeostasis. The transcription factor 7-like 2 (TCF7L2) gene is a member of the T-cell factor (TCF)/lymphoid enhancing factor family which encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The key effector of the canonical Wnt signaling pathway (defined as Wnt pathway hereafter) is the bipartite transcription factor β-cat (β-catenin)/TCF, formed by β-cat and a member of the TCF family [TCF-1/TCF7, LEF-1, TCF-3/TCF7L1 and TCF-4/TCF7L2]. In the absence of Wnt signaling, these HMG box TCF proteins function in the nucleus as transcriptional repressors of the Wnt target genes. TCF7L2 gene is located in chromosome 10q25.3, spans 215.9 kb and contains 14 exons (NCBI build 36.2). However, a previous study has shown that TCF7L2 has 17 exons, of which five are alternative splicing. Genetic variants of gene are associated with increased risk of type 2 diabetes. Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with Type 2 Diabetes all population. The prevalence of Type 2 Diabetes shows wide ethnic and geographic variations. In this study, we analyzed three polymorphisms in the TCF7L2 gene, rs12255372, rs11196205 and rs7901695 using a case-control design in 163 individuals (113 unrelated T2DM patients and 50 normoglycemic controls) to assess their association with T2DM risk in the Turkish population.

Transcription factor 7-like 2 (TCF7L2) gene polymorphisms are strong predictorsof type 2 diabetes among nonobese diabetics in the Turkish population.

Type 2 diabetes (T2D) is1397645907a multifactorial disease, determined by environmental and genetic factors. Currently, the transcription factor 7-like 2 (TCF7L2) gene shows the strongest association with T2D. In this study, we investigated whether TCF7L2 gene polymorphisms are associated with T2D in a Turkish population. Using PCR-RFLP and PCR-SSCP, we genotyped six intronic polymorphisms in the TCF7L2 gene, commonly associated with T2D, in 169 individuals with diabetes and 119 healthy controls. We found that rs7903146 C → T substitution in intron 3 (OR: 1.9, P = 0.005) and rs12255372 G → T substitution in intron 4 (OR: 2.1, P = 0.002) were significantly associated with T2D while other SNPs were not associated (P > 0.05). We determined no association between TCF7L2 gene polymorphisms and fasting glucose, fasting insulin, HbA1c, or HOMA-IR levels (P > 0.05), except for rs7903146 C → T substitution, which was significantly associated with the fasting glucose level (P = 0.003). Our results indicate that, in the Turkish population, the T allele of the rs7903146 (C → T) and rs12255372 (G → T) polymorphisms in the TCF7L2 gene is an independent risk factor for the development of T2D.

Role of GNB3, NET, KCNJ11, TCF7L2 and GRL genes single nucleotide polymorphism in the risk prediction of type 2 diabetes mellitus.

Type 2 diabetes (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion or insulin resistance. Various environmental and genetic factors interact and increase the risk of T2DM and its complications. Among the various genetic factors associated with T2DM, single nucleotide polymorphism in different candidate genes have been studied intensively and the resulting genetic variants have been found to have either positive or negative association with T2DM thereby increasing or decreasing the risk of T2DM, respectively. In this review, we will focus on Guanine nucleotide-binding protein subunit beta 3 (GNB3), Norepinephrine Transporter (NET), Potassium Channel gene (KCNJ11), Transcription Factor 7-Like 2 (TCF7L2) and Glucocorticoid receptor (GRL) genes and their association with T2DM studied in different ethnic groups. The products of these genes are involved in the biochemical pathway leading to T2DM. Polymorphisms in these genes have been intensively studied in individuals of different ethnic origins. Results show that genetic variants of TCF7L2 and KCNJ11 genes have potential to emerge as a risk biomarker for T2DM whereas results of GNB3, GRL and NET genes have been controversial when studied in individuals of different ethnicities. We have tried to summarize the results generated globally in context to the selected genes which could possibly help researchers working in this field and would eventually help in understanding the mechanistic pathways of T2DM leading early diagnosis and prevention.

Association between rs7901695 and rs7903146 polymorphisms of the TCF7L2 gene and gestational diabetes in the population of Southern Poland.

The etiology of gestational diabetes mellitus (GDM) remains to be fully elucidated. Elevated risk for type 2 diabetes in patients with history of GDM and for GDM in women with familial history of diabetes may suggest that GDM and type 2 diabetes share a common genetic and environmental background. The TCF7L2 (Transcription Factor 7 Like 2) gene is one of the most important genetic factors of the established correlation with type 2 diabetes, and it may also play a role in the pathophysiology of GDM. The aim of the study was to assess the influence of two polymorphisms of the TCF7L2 gene (rs7901695 and rs7903146), which are associated with the development of type 2 diabetes, in women with GDM. The study included 50 women with glucose tolerance disorders diagnosed for the first time during the current pregnancy. Single nucleotide polymorphisms (SNPs) were genotyped using allelic discrimination. The results were confirmed using the sequencing method. Selected clinical parameters were also analyzed. No correlation between the studied polymorphisms of the TCF7L2 gene and GDM was observed. Glycemic control with diet or diet and insulin was associated with better control of the weight gain during pregnancy. No correlation between rs7903146 and rs7901695 polymorphisms of the TCF7L2 gene and GDM was found. Glycemic control with diet or diet and insulin is associated with better control of the weight gain during pregnancy.

Common variants in TCF7L2 and CDKAL1 genes and risk of type 2 diabetes mellitus in Egyptians.

In this work we studied association of common variants in transcription factor 7-like 2 (TCF7L2) and cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) genes with type 2 diabetes mellitus (T2DM) in Egyptians.Subjects and methodsThis is a case–control study; 180 T2DM patients and 210 control subjects were genotyped for TCF7L2 rs7903146 and rs12255372 and CDKAL1 rs7756992 single nucleotide polymorphisms (SNPs) by TaqMan method on real time polymerase chain reaction system (real time-PCR).ResultsTCF7L2 rs12255372 and rs7903146 associated with T2DM (p = 0.0001 and 0.003; respectively). The rs12255372 variant T allele associated with 2-fold increased risk for T2DM and TT genotype carriers were at 3.58-folds higher risk to develop T2DM than wild genotype (GG) carriers. Meanwhile, rs7903146 variant T allele associated with 1.6-fold increased risk for T2DM and TT genotype carriers were at 2.3-folds higher risk than wild genotype (CC) carriers. Both TCF7L2 SNPs significantly associated with T2DM under additive and dominant models and after adjustment for other covariates. On the other hand, CDKAL1 rs7756992 showed no significant association with T2DM under any genetic model. Both TCF7L2 SNPs were in strong LD (P = 0.02; D′ = 0.85). Taking common TCF7L2 rs12255372/rs7903146 GC haplotype as reference, multivariate analysis confirmed the association of rs12255372 T allele-containing haplotypes (TC and TT) with T2DM. Haplotype TC associated with 6.32 times-higher risk for T2DM (95%CI = 0.55–76.17, Pc = 0.04) followed by haplotype TT which associated with 3.88 times-higher risk for the disease (95%CI = 1.09–13.76, Pc = 0.03).ConclusionTCF7L2 rs12255372 and rs7903146 common variants associate with T2DM risk in Egyptians.

Polymorphisms in TCF7L2 gene are associated with gestational diabetes mellitus in Chinese Han population

This study aimed to investigate the possible association between diabetes susceptibility gene transcription factor 7-like 2 (TCF7L2) and gestational diabetes mellitus (GDM) in a Chinese Han population. A total of 556 GDM patients and 500 Non-GDM were included. Eighteen single nucleotide polymorphisms (SNPs) were evaluated. Fifteen tag SNPs were selected from HapMap CHB database with a minor allele frequency of >0.2 and r2 of >0.8. Three additional SNPs were also chosen because these SNPs are associated with type 2 diabetes in East Asians. TCF7L2 rs290487, rs6585194, and rs7094463 polymorphisms were found to be significantly associated with GDM. In multivariate analysis, rs290487 genetic variation (OR = 2.686 per each C allele, P = 0.002), pre-BMI > 24 kg/m2 (OR = 1.592, P = 0.018), age > 25 years (OR = 1.780, P = 0.012) and LDL-C > 3.6 mmol/L (OR = 2.034, P = 0.009) were identified as independent risk factors of GDM, rs7094463 genetic variation (OR = 0.429 per each G allele, P = 0.005) was identified as independent protect factor of GDM. This finding suggests that TCF7L2 rs290487, and rs7094463 were a potential clinical value for the prediction of GDM.

TCF7L2 polymorphism is associated with low nitric oxide release, endothelial dysfunction and enhanced inflammatory response after myocardial infarction

BackgoundThe favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is associated with attenuated insulin secretion. MethodsIn non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%β) and insulin sensitivity (HOMA2%S). ResultsAlthough glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%β and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality. ConclusionIn non-diabetic STEMI patients, the rs7903146 TCF7L2 gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality. General significanceDuring the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.

Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes.

BackgroundThe rs7903146-T allele in the transcription factor 7-like 2 (TCF7L2) gene has been associated with impaired pancreatic insulin secretion, enhanced liver glucose production, and an increased risk of type 2 diabetes. Nevertheless, the impact of rs7903146 on daily glucose trajectories remains unclear. Continuous glucose monitoring (CGM) can estimate glycemia and glycemic variability based on consecutive glucose measurements collected over several days. The purpose of the present study was to investigate the associations of rs7903146 with glycemia and glycemic variability in middle-aged participants without diabetes.MethodsComplete data from 235 participants without diabetes from the Leiden Longevity Study were available. Participants were divided into two groups based on rs7903146 genotype; rs7903146-CC genotype carriers (N = 123) and rs7903146-CT/TT genotype carriers (N = 112). Validated parameters of glycemia (e.g., mean 24h glucose level) and glycemic variability (e.g., 24h standard deviation) were derived from data collected with a CGM system for a 72-hour period.ResultsThe study population was on average 64.7 years old (standard deviation = 5.9) and composed of 49.8% of women. Compared with rs7903146-CC carriers, rs7903146-CT/TT carriers exhibited a trend towards a higher mean 24-hour glucose level (5.21 versus 5.32 mmol/L; p-value = 0.15) and a significantly higher mean nocturnal glucose (3:00am– 6:00am; 4.48 versus 4.67 mmol/L; p-value = 0.03) that was explained for 34.6% by body weight and percentage body fat. No differences in measures of glycemic variability between the genotype groups were observed.ConclusionDespite limited sample size, our study indicates that the rs7903146-T allele in TCF7L2 was associated with a higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of glucose metabolism.

Polymorphism of Transcription Factor 7-Like 2 Gene and HOMA-β Level of Individuals With and Without Type 2 Diabetes Mellitus Family History

Family history has considered as a risk factor of type 2 diabetes. Transcription factor-7 like 2 (TCF7L2) hasrole to regulates insulin secretion and blood glucose homeostasis. The aim of current study was to determine thers7903146 polymorphism of TCF7L2 gene and homeostatic model assessment-β (HOMA-β) level on individual withand without type 2 Diabetes Mellitus (DM) family history. This work is a case-control study. Thirty six subjectswith type 2 DM family history and 36 subjects without type 2 DM family history were recruited. HOMA-βmeasure to analyze the insulin secretion. Polymorphisms of TCF7L2 gene was analyzed by using PCR-RFLPmethod. Statistical analysis was performed by using T-test, Mann-Whitney and Chi-square with signifi cancelevel 0.05. The frequency of the T allele of the cases were 4.2% and the controls were 2.8% (p=0.500). The oddratio was 0.649 (CI;95%:0.106-4.055). The HOMA-β levels of the cases were signifi cant low (132.56±62.48)compared with the controls (266.09±1.68) with p=0.000. The subjects with type 2 DM family history have asimilar frequency of having T alleles and CT/TT genotypes. The subjects with type 2 DM family history hassignifi cantly lower HOMA-β levels than subject without DM family history.