The transcription factor 7-like 2 gene (TCF7L2) is an element of the Wnt signaling pathway. There is lack of evidence if TCF7L2 has a functional role in lipid metabolism and regulation of the components constitutes the metabolic syndrome (MetSyn).The aims of this study were to evaluate whether the risk allele of TCF7L2 gene polymorphism is associated with dyslipidemia and MetSyn.
The MetSyn subjects were participated only based on the National Cholesterol Education Program – Third Adult Treatment Panel criteria. In this case–control study, the DNA from MetSyn patients without (n = 90) and with type 2 diabetes (T2D) (n = 94) were genotyped.
The results show that the genotype-phenotype for CC, CT/TT of TCF7L2 gene polymorphism correlated with body mass index and waist circumference in MetSyn and MetSyn T2D subjects (r = ?0.949 and r = ?0.963, respectively). The subjects that only possess MetSyn but are not diabetics show the 2 h postprandial glucose and fasting blood glucose, glycated hemoglobin significantly lower (P The results revealed the important insights essential for the role of TCF7L2 that the T allele of TCF7L2 plays a significant role in the susceptibility to dyslipidemia, MetSyn, and T2D.

Several previously published reports have suggested a relationship between type 2 diabetes mellitus (T2DM) and chromosome 10q. The results of genotyping of 228 microsatellite markers in Icelandic people with T2DMrevealed that a microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with T2DM. The present study was aimed to analyze the sequence of TCF7L2 in Iraqi patients with T2DM. This study was performed on the blood samples of 10 patients within the age range of 18-70 years old with T2DM. The DNA was extracted from the whole blood samples and the TCF7L2 gene was purified and amplified using the polymerase chain reaction (PCR) technique. Afterward, the PCR products were run in gel electrophoresis to detect the gene. Moreover, the BLAST software was used to analyze the gene TCF7L2 sequence which was compared with the reference sequence of the template gene from NCBI. The results of TCF7L2 gene sequences obtained from the samples collected from the Iraqi patients with T2DMwere received from Macogen Company, Korea, and analyzed using the BLAST software. The findings showed mutations in the gene sequence of all patients, compared to the gene sequences in NCBI. Hence, the mutation in the TCF7L2 gene was present in Iraqi patients with T2DM, and it could be one of the factors causing and increasing the risk of T2DM disease.

Enhanced glucose production by the liver contributes to hyperglycemia in individuals with diabetes. The purpose of this research was to explore how resistance training influences serum insulin levels, fasting glucose, insulin sensitivity, and TCF7L2 gene expression in the liver cells of rats with type 2 diabetes (T2D). To achieve this aim, T2D was induced in 14 male Wistar rats, aged 10 weeks, through an 8-week high-fat diet combined with streptozotocin (STZ) administration. Subsequently, these rats were randomly divided into two groups: an exercise group that underwent resistance training for 8 weeks, five times per week (n = 7), and a control group that did not receive any training (n = 7). 48 hours following the final training session, all rats underwent dissection. Measurements were taken for TCF7L2 gene expression, glucose, insulin, and insulin resistance, and these metrics were statistically analyzed using an independent t-test between two groups. The data indicated that, relative to the control group, resistance training significantly reduced glucose levels (P = 0.001) and insulin resistance (P = 0.009), while it increased serum insulin levels (P = 0.035) and TCF7L2 gene expression in hepatocytes (P = 0.011). Based on these finding, improved glucose and insulin resistance following resistance training in T2D can be attributed to enhance TCF7L2 gene expression in hepatocytes by training.

Resistance exercise is recommended as a useful therapeutic tool for the treatment of type 2 diabetes (T2D); however, the frequency of studies is inadequate to establish the precise mechanisms of any association between them.
In this study, we aimed to assess the effect of three months of resistance training on TCF7L2 expression in pancreatic tissues, serum insulin and glucose.
For this purpose, type 2 diabetes (T2D) was induced by intraperitoneal streptozotocin-nicotinamide in eighteen male Wistar rats aged 10 weeks (220 ± 30 g). Then, the rats were randomly divided into exercise and control groups. The exercise rats completed a three-month resistance training intervention that included climbing on a stepladder for 5 days weekly. The control group did not participate in exercise intervention. Fasting glucose and insulin were measured before and after injection (7 days) and after intervention. TCF7L2 gene expression of pancreatic tissues was measured in both groups after the exercise treatment, and the ratio between the two groups was calculated.
Fasting glucose increased and serum insulin decreased significantly by T2D induction in the two groups at baseline. Resistance training resulted in a decrease in fasting glucose and an increase in insulin in exercise rats. Data also showed that TCF7L2 gene expression decreased after resistance training compared with the control group.
Based on these data, increased serum insulin can be attributed to a decrease in TCF7L2 gene expression of pancreatic cells by resistance training in T2D rats.

Background TCF7L2 gene encodes a transcription factor that plays an important role in the Wnt signaling pathway. In this pathway TCF7L2 protein induces transcription of genes involved in glucose homeostasis, such as intestinal proglucagon. The aim of present study was to investigate the association of rs12255372, and rs290487 polymorphisms of TCF7L2 with T2DM in Arab ethnic of Khuzestan province in Iran.
Methods 100 patients with T2D and 97 normoglycemic subjects were included in this study. The PCR-RFLP and TETRA ARMS- PCR technique, subsequently validated by direct sequencing, was used for genotyping.
Results A significant difference in TT genotype was observed between two groups patient and control (OR=4.12, 95%CI=1.55-10.55, P=0.005). Also T allele frequencies of rs12255372 was different in the groups (0R=1.69, 95%CI=1.12-2.53, p=0.02). No allelic or genotypic association with T2D was detected for rs290487.
Conclusion Our finding suggest that TT genotypes rs12255372 confers an increased risk of developing T2D. The rs290487 is unlikely an influential variant with type 2 diabetes in this population.

Objective :

Hepatic glucose release is greatly increased in the presence of obesity and related diseases. The research objective was to explore the impact of high intensity interval training (HIIT) on TCF7L2 gene expression in hepatocytes of obese rats.

Out of 21 male Wistar rats aged 10 weeks years (220±10 g), obesity was induced in 14 rats by 8-week high-fat diet. The rats were then divided into normal (n=7), obese control (n=7), and HIIT obese (n=7) groups. Rats in the HIIT group completed 8 weeks of HIIT/5 days weekly, whereas the other groups were inactive. After intervention, TCF7L2 gene expression in hepatocytes, insulin resistance and glucose compared using ANOVA /Tukey’s post hoc test between groups by SPSS-22.

Obesity induction led to a significant decrease in TCF7L2 gene expression (P: 0.011) and an increase in blood glucose (P: 0.009) and insulin resistance (P: 0.019) compared with the normal group (P< 0.001). On the other hand, interval training led to a significant increase in TCF7L2 gene expression (P: 0.029) and a decrease in blood glucose (P< 0.001) and insulin resistance (P< 0.001) in the obese group compared with the control group.

The observed enhancement in fasting blood glucose levels among obese rats could be linked to increased TCF7L2 gene expression in liver cells, which appears to be a response to interval training intervention. Nevertheless, understanding the main mechanisms responsible for observed changes requires further studies in this field.

Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146; however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10-2) to strong association in European descent populations (P= 2.0×10-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.

Type 2 diabetes mellitus (T2DM), one of the costliest chronic diseases of our time, is a multifactorial and heterogenic disease with a complex etiology. Among all the T2DM related genes, the SNPs of the transcription factor 7-like 2 (TCF7L2) gene have been recognized as the strongest genetic risk factors for T2DM in different ethnic groups by several studies. The aim of this study was to investigate the possible association between TCF7L2 gene polymorphisms (rs290487, rs11196205, rs7903146, and rs12255372) and the risk of T2DM in a population from Khuzestan province, South-West of Iran.

In this case-control association study, we studied 146 patients with T2DM and 146 healthy subjects. Genotyping for rs290487 and rs11196205 were done by Tetra-Primer ARMS-PCR and genotyping for rs7903146 and rs12255372 were carried out using PCR-RFLP. Statistical analyses were carried out using SPSS v.25.

For rs290487 polymorphism, TT and TC genotypes were not observed in patients and controls, and all of the subjects showed only CC genotype. The C allele of rs11196205 polymorphism was associated with T2DM (OR = 1.393, 95% CI = 1.005-1.932, p-value = 0.046). Two other studied polymorphisms, rs7903146 and rs12255372, had no significant differences in the genotype and allele frequencies between the two groups. Three-variant haplotypes of TCF7L2 gene were analyzed using the PHASE software. There was no significant difference between control group and case group for haplotype distribution.

Our results suggest that there is a significant association between rs11196205 polymorphism and T2DM, but no association is observed between the three other polymorphisms (rs290487, rs7903146, and rs12255372) with T2DM in the studied population. Moreover, no risk haplotype is reported in our population.

Diabetes as a heterogeneous disease is characterized by a decrease in insulin sensitivity and a defect in insulin secretion. In general, diabetes is divided into four groups, type 1 diabetes, type 2 diabetes, gestational diabetes, and diabetes of various causes. To be Emerging evidence suggests that common and rare genetic polymorphisms can influence the risk of diabetic complications. Type 2 diabetes is a heterogeneous group of disorders that is usually characterized by the inability of pancreatic beta cells to increase insulin secretion to compensate for insulin resistance in peripheral tissues. Type 2 diabetes has been diagnosed in adults and is related to obesity, lifestyle, age, family history, and genetics. Genetically, many gene polymorphisms are known to be associated with this disease. The cause of type 2 diabetes is a mixture of lifestyle and genetic factors, while a person can control some of these issues such as diet and obesity, other issues such as aging, being female, and genetics cannot be controlled. However, until now, the exact cause of this disease has not been determined and its prevalence rate is also increasing. In the last decade, the prevalence of this disease has increased alarmingly in Iran. The single nucleotide polymorphism 7903146rs is located in intron number 3 of the TCF7L2 gene, which is significantly associated with type 2 diabetes. The expression of TCF7L2 in pancreatic cells of type 2 diabetic patients compared to healthy individuals was reported to be accompanied by a decrease in insulin secretion. Apart from the effect of the TCF7L2 variant on cell structure and insulin release from the beta pancreas, several studies have also reported a decrease in insulin secretion in response to the increased expression of TCF7L2 in the pancreas. The TCF7L2 gene is a transcription factor involved in the Wnt signaling pathway, which plays an important role in the development of pancreatic islets and fat. The TCF7L2 gene is considered one of the most important candidate genes for T2DM and plays an important role in blood glucose homeostasis and function. It has beta cells. The rs7903146 variant is one of the most important variants that has been proven to be related to diabetes in other populations, but so far no study has been conducted in East Azerbaijan on the relationship between the role of TCF7L2 in the development of type 2 diabetes, so the present study aims to investigate the relationship between poly The Morphism of rs7903146 in the TCF7L2 gene was performed in patients with type 2 diabetes in East Azerbaijan.

101 unrelated patients were invited to the diabetes clinic to provide blood samples. The basic information of the patients such as BMI, gender, and age was recorded in a questionnaire, and to comply with the ethical principles, a tracking code was inserted at the top of each questionnaire. Also, 101 unrelated healthy people were selected from the general population to call the control subjects. In this study, about 2 cc of blood samples were taken from each person and collected in tubes containing EDTA. The collected samples were transferred to the laboratory with a flask containing dry ice and kept at -20°C until extraction. The tubes containing the blood samples of patients and controls were numbered separately, and their gender was also noted on the tubes. After DNA extraction from all samples and quality assessment of the samples with specific primers, PCR and electrophoresis were performed. Took finally, the PCR products were treated with RSal restriction enzyme and electrophoresed again, and the target polymorphism was checked.

The frequency of genotypes was found as TT=33.7, CC=16.8, and CT=49.5 (percentage) for healthy people and the frequency of genotypes in sick people was found as TT=43, CC=14, and TC=43. = (percentage) was calculated. The percentage of the T allele in healthy and sick people was reported as 42.1% and 64.5%, respectively, and the percentage of the C allele in healthy and sick people was reported as 57.9% and 35.5%, respectively.

Because today diabetes is spreading all over the world as an unprecedented epidemic and also considering the role of genetic factors in the development of type 2 diabetes, it is necessary to investigate the genes related to this disease. It seems in the present study, the results showed that the frequency of the C allele, which is the dominant allele, is 57.9% in the healthy group, and 35.5% in the patient group, which shows a 22% decrease, and the frequency of the T allele, which is the polymorphism allele. It is 42.1% in the healthy group and 64.5% in the patient group, which 22% increase in the patient group shows that there is probably a relationship between the increase of the T allele and the risk of type 2 diabetes and the risk The incidence rate in the patient group is 2.501, and since it is more than one, there is a risk of contracting the disease, while the risk rate in the healthy group is 638.00, which is less than one. On the other hand, the frequency of genotypes was found as TT=33.7, CT=16.8, and CC=49.5 (percentage) for healthy people, and in sick people, the genotype frequency was as TT=43, CC=14, and TC = 43 (percentage) was calculated. The results of this study show that the types of polymorphisms are a factor for genetic diversity and determine the phenotypic diversity between people, and it may affect the susceptibility of people to diseases and the progression of diseases and polymorphisms. A gene shows a significant relationship with the probability of diabetes. In this study, the possibility of the association of rs7903146 polymorphism with diabetes has been determined, so it can be said that rs7903146 polymorphism can be used as an indicator and marker to detect the susceptibility to diabetes in other research, and considering that this polymorphism Gene Morphism shows a different frequency distribution in different regions, it seems that studying target gene variants in different populations to find their relationship with diabetes is important.

Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a class II membrane glycoprotein that binds to insulin α receptor and can interfere in insulin signaling pathway. Transcription factor-7-like 2 (TCF7L2) is a transcription factor which plays a critical role in pancreatic β cell activity. ENPP1 and TCF7L2 gene polymorphisms may have functional role in susceptibility to type2 diabetes (T2D). The aim of this study was to investigate the association of reported K121Q and C/T rs7903146 variants of ENPP1 and TCF7L2 genes with the risk of T2D in our population 240 T2D and 240 healthy subjects were recruited. Genotyping was carried out by PCR-RFLP method. T test was used for association study. ENPP1 121Q (CC) genotype was significantly higher in T2D comparing to controls (OR;1.61, 95% CI;1.02-2.55, P=0.02) and a significant association between the frequency of C allele and T2D was observed (OR;1.339, 95%CI;1.04-1.72, P=0.012). TT genotype of TCF7L2 C>T rs7903146 was significantly higher in T2D patients (OR;0.67, 95% CI;0.49-0.98, P=0.02), but the T allele could not significantly affect the risk for T2D in our population. The high frequency of Q allele of the ENPP1 K121Q and TT genotype of the TCF7L2 might be considered as a predisposing factor for T2D.