Genomic Study of TCF7L2 Gene Mutation on Insulin Secretion for Type 2 DM Patients: A Review

Aim: This paper aims to establish whether a correlation between TCF7L2 gene mutation on insulin secretion for Type 2 DM Patients. Background: Diabetes type 2 is the most common metabolic disorder worldwide. Beta cell dysfunction reduces insulin secretion and increases the glucose level in the blood and insulin resistance that raises the glucose production in the liver and decreases the glucose uptake to muscle, liver, and adipose tissue causing hyperglycemia (T2DM). TCF7L2 (transcription factor 7杔ike 2) works as a nuclear Receptor for CTNNB1(B catenin) that mediated the WNT signaling pathway (a group of signal transduction pathways made of proteins that pass signals from outside a cell through cell surface receptors to the inside of the cell) and any variation will cause the development of T2DM. Methods: GenBank in NCBI database was used to extract the DNA sequence and mRNA sequence of the TCF7L2 gene (an accession number of the gene, number of amino acids, exons, and length of nucleotides). FASTA format was also useful to retrieve the nucleotide sequence and get the function of the protein. BLAST was used to compare the protein product of the TCF7L2gene between humans and gorillas, and pygmy chimpanzees (Pan paniscus). Results: The accession number is NC_000010.11, the number of amino acids in the protein product is 602, the number of exons found is 20 and the gene is in chromosome 10. Finally, many organisms have the same gene as dogs, cows, mice, rats, zebrafish, and frogs. Conclusion: There is a strong association between TCF7L2 (transcription factor 7杔ike 2) alleles (rs7903146) T alleles and T2DM. It was found that there is a high frequency of diabetic type two patients having TCF7L2 (transcription factor 7杔ike 2) alleles (rs7903146) with a high frequency of the T allele

rs7903146 mutation of Type 2 diabetes mellitus-related gene TCF7L2 is not associated with polycystic ovary syndrome in a cohort of Turkey

SUMMARY OBJECTIVE The aim of this study was to investigate whether TCF7L2 gene mutation rs7903146 is in association with polycystic ovary syndrome (PCOS). METHODS A total of 44 PCOS and 48 control participants were recruited for this study. After DNA extraction from peripheral blood, quantitative PCR method was used for genotyping. With a case-control study design, two groups were compared for genotype and allele frequencies as well as clinical characteristics. RESULTS Mean testosterone level was significantly higher in PCOS group, whereas mean progesterone level was significantly higher in control group. In PCOS group, mean thyroid-stimulating hormone (TSH) level was significantly higher in polymorphic allele carriers. Genotype and allele frequencies were not different between groups. CONCLUSIONS When investigated for the first time in a population from Turkey, no association between PCOS and TCF7L2 gene rs7903146 polymorphism was detected. However, considering contradictory results of other populations and low cohort scale of this study, replication studies with greater cohorts are needed.

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<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.

Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

Background: Genetic predisposition plays a critical role in the incidence of type 2 diabetes mellitus (T2DM). While a few reports strongly associate TCF7L2 gene polymorphisms in the T2DM incidence in India, data pertaining to the prevalence of these polymorphisms in the south Tamil Nadu population has been lacking. Hence, the present study aims to determine the prevalence and association of the TCF7L2 gene variants rs7903146, rs12255372 in the regional population of south Tamil Nadu.Methods: Peripheral blood samples from controls, T2DM patients were utilized to isolate genomic DNA and genotyping was carried out using PCR based strategies, direct sequencing. Socio-demographic details, anthropometric measurements, determination of postprandial, random blood glucose levels and oral glucose tolerance test (OGTT) were further carried out to evaluate the predisposition risk for T2DM.Results: 50% of the control group participants and 73.9% of the T2DM patients were positive (CT/TT) for the TCF7L2 polymorphism rs7903146. The rs12255372 SNP was less prevalent in the controls, patients and was dispersed in only 25% of the controls and 60.9% (GT/TT) of the patients. The 60 minutes plasma glucose levels for the oral glucose tolerance test (OGTT) was higher (143.3±19.8) in the rs7903146 and rs12255372 positive control participants.Conclusions: The study results reveal that TCF7L2 polymorphisms are dispersed in the regional population and further large scale, long term follow up studies will aid preventive and therapeutic measures in T2DM.

Role Of Capn-10, Tcf7l2, Ppar Gandkcnj11gene In Type 2 Diabetes Mellitus (t2dm)

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by polygenic hyperglycemia caused by insulin secretion or insulin resistance. Several environmental factors and genetics interact to increase the risk of developing type 2 diabetes and its complications. Among the various factors associated with genetic T2DM polymorphism of the same nucleotide in several genes, it has been widely studied and showed that the resulting genetic variants have a positive or negative correlation with T2DM, which increases or decreases the risk of T2DM. In this review, we will focus on the Peroxisome proliferator-activated receptor gamma (PPARG), Potassium voltage-gated channel subfamily J member 11 (KCNJ11), Transcription factor 7-like 2 (TCF7L2), Calpain-10 (CAPN10) and their relationship with T2DM, studied in different ethnic groups. The products of these genes are involved in the biochemical pathway leading to T2DM. The polymorphisms of these genes are widely studied in individuals of different ethnic groups. The results show that the genetic variants of the CAPN-10, TCF7L2, PPARG, and KCNJ11 genes can become a biomarker of risk for T2DM, and were studied in people from different ethnic groups. We tried to synthesize globally obtained results in the context of selected genes that could help researchers working in this area and ultimately it would be helpful to understand the mechanistic pathways of T2DM lead to early diagnosis and prevention.

TCF7L2 gene variant rs7903146 affects the risk of Type 2 Diabetes by modulating incretin secretion

Background: Type2 diabetes mellitus (T2DM) is a highly inheritable disease. Transcription factor 7- like 2 (TCF7L2) gene regulates the expression of glucagon-like peptide 1 (GLP-1) in L cells of small intestine. GLP1 plays a critical role in blood glucose homeostasis by stimulating postprandial insulin secretion and increasing insulin sensitivity. Aim of the study: TCF7L2 gene variants may affect the susceptibility to Type 2 diabetes by altering GLP-1 levels. Materials and methods: This case-control study was conducted with 90 newly diagnosed patients with Type2 diabetes mellitus as cases and 90 age and sex-matched healthy volunteers as controls. TCF7L2 rs7903146 genotyping was done and we also estimated Fasting and postprandial GLP -1 level, Fasting and Postprandial insulin level and calculated HOMA-IR in both cases and controls. Results: Out study showed that T+ genotype, lower fasting GLP-1 level and lower postprandial GLP1 levels were more observed among cases as compared to controls. Low mean GLP 1 activity, high Mean HOMA-IR, low postprandial insulin, low percentage rise in insulin were observed among T+ genotype than among T- genotypic individuals. Conclusion: Hence, the study concludes that T+ genotype causes a decrease in GLP-1 levels, which in turn by decreasing postprandial insulin levels and by increasing insulin resistance increases the risk of Type2 diabetes.

Effect of activated canonical wnt/p-catenin/tcf7l2 signaling pathway in type 1 diabetic cardiomyopathy / 中国药理学通报

Aim To determine the role of Wnt/β-catenin/TCF7L2 pathway in diabetic cardiomyopathy.Methods A model of type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin(STZ)into 7 or 8-week old C57BL/6 mice.After four weeks, the diabetic animals were divided into three groups with seven to eight in each:diabetes mellitus(DM), diabetes injected with β-catenin inhibitor iCRT14(2.5, 5 mg·kg-1).After continuous intrap-eritoneal administration for 8 weeks, heart samples were stained with HE and examined under light microscopy.Expressions and distributions of β-catenin and TCF7L2 in myocardium were detected by immunohistochemistry.Protein levels of β-catenin, Tcf7l2 were detected by Western blot.mRNA levels of β-catenin, Tcf7l2, Nppa and c-Myc were detected by qPCR.Results The myocardial cells in DM were relatively disordered and the size of the nucleus was irregular.Western blot and immunohistochemistry data showed that the expressions of β-catenin and TCF7L2 in heart with DM increased, while those in nucleus of the cardiomyocytes significantly increased.qPCR showed that the mRNA expression of β-catenin downstream target c-Myc and cardiac hypertrophy marker Nppa were up-regulated.After injection of eight weeks with different iCRT14 doses, the cardiomyocytes were relatively regular; the protein levels of β-catenin and TCF7L2 decreased, and their expressions in nucleus decreased as well; the mRNA levels of Nppa and c-Myc markedly decreased.Conclusions Activation of canonical Wnt/β-catenin/TCF7L2 signaling pathway plays a pivotal role in diabetic cardiomyopathy; iCRT14 significantly improves the phenotype of cardiomyopathy in type 1 diabetic mice.

LncRNA TCF7 promotes malignant biological behavior of lung cancer cells by regulating miR-29 and activating JAK/STAT2 signaling pathway / 国际生物医学工程杂志

Objective To investigate the malignant biological behavior and mechanism of LncRNA TCF7 in lung cancer cells by regulating miR-29 and activating JAK/STAT2 signaling pathway.Methods qPCR was used to detect the expression of TCF7 and miR-29 in lung cancer tissues and different lung cancer cell lines.The relationship between TCF7 and clinicopathological data of lung cancer patients was analyzed.The dual luciferase reporter assay was used to detect the interaction between TCF7 and miR-29.MTT proliferation assay and Transwell invasion assay was used to detect the proliferation and invasion of lung cancer cells after inhibition of TCF7,respectively,and to analyze the relevant recovery after the overexpression of miR-29.The expression of JAK/STAT2 signaling pathway protein was detected by Western Blotting after TCF7 inhibition.The effect of TCF7 on tumor formation in vivo was detected by in vitro tumor formation assay in nude mice.Results Compared with other lung cancer cell lines,A549 cells had the highest expression of TCF7 and miR-29.The expression of TCF7 was associated with the pathological stage of lung cancer and lymph node metastasis,in which TCF7 was positively correlated with cancer stage and lymph node metastasis.The dual luciferase assay confirmed that TCF7 can specifically bind to the target of miR-29,and regulate the expression and activity of miR-29.The inhibition of the expression of TCF7 can promote the proliferation and invasion of lung cancer cells.After inhibiting the expression level of miR-29,the proliferation and invasion ability of lung cancer cells were partly restored.After inhibiting the expression of TCF7,JAK/STAT2 signaling pathway was activated accordingly.Compared with the non-small carcinoma group,the average tumor volume and mass of the transplanted tumor in the TCF7-siRNA group were reduced.Conclusions TCF7 can regulate the expression of miR-29 and affect the proliferation and invasion of lung cancer cells through JAK/STAT2 signaling pathway.

Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans

Objective The global burden of diabetes mellitus will impact strongly American countries in the coming decades. Type 2 diabetes mellitus (T2DM) is a multifactorial disease and the basis for its genetic susceptibility remains not fully understood. Different population studies have demonstrated that variants of the TCF7L2 gene are strongly associated with an increased risk of T2DM. Moreover, institutions or countries with limited budget to conduct genetic research need cost effective methods for detecting DNA variants. Subjects and methods We standardized a rapid and simple allele-specific PCR method for genotyping the rs12255372 single nucleotide polymorphism (SNP) in a pilot study exploring the association of three TCF7L2 polymorphisms (rs7903146, rs12255372 and DG10S478) with T2DM in 70 patients and 73 controls from Venezuela. Results The performance of the designed allele-specific PCR reaction for rs12255372 genotyping was reliable and accurate. Patients carrying the TCF7L2 rs7903146 T allele (CT + TT genotypes) and heterozygous CT genotype had a significantly higher risk for T2DM (OR = 2.9 and 2.3, respectively). Although rs12255372 and DG10S478 risk alleles predominated in T2DM group no statistical significance was found. Conclusions We developed a novel allele-specific PCR method for easier and rapid detection of rs12255372 polymorphism without the use of expensive instrumentation and reagents. Our study in a relatively small sample of the Venezuelan population replicated the association of the rs7903146 SNP with T2DM. Further studies with larger sample size and more biochemical data should be conducted to explore the genetic basis of T2DM susceptibility in Venezuela.

The association between the rs11196218A/G polymorphism of the TCF7L2 gene and type 2 diabetes in the Chinese Han population: a meta-analysis

Transcription factor 7-like 2 has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups in recent years. In the Chinese Han population in particular, numerous studies have evaluated the association between the rs11196218A/G polymorphism of the transcription factor 7-like 2 gene and type 2 diabetes mellitus. However, the results have been inconsistent, so we performed a meta-analysis to assess the association. Odds ratio and 95% confidence interval values were calculated using a random-effects model or a fixed-effects model based on heterogeneity analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Subgroup analyses were conducted based on conformity with Hardy-Weinberg equilibrium in the control group as well as on other variables, such as age, sex and body mass index. Sensitivity analysis was also performed to detect heterogeneity and to assess the stability of the results. In total, 10 case-control studies comprising 7,491 cases and 12,968 controls were included in this meta-analysis. The combined analysis indicated that the rs11196218A/G polymorphism was not associated with type 2 diabetes mellitus (G vs. A, OR=1.04, 95% CI=0.97–1.13, p=0.28). The subgroup analyses also did not show any association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus. Furthermore, the results of the subgroup analyses indicated that the absence of an association was not influenced by age, sex or body mass index. The results of the sensitivity analysis verified the reliability and stability of this meta-analysis. In conclusion, this study indicated that there is no significant association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus in the Chinese Han population.

Relationship between genetic polymorphism of transcription factor 7-like 2 and genetic susceptibility to type 2 diabetes mellitus in Uygur population of Xinjiang region / 基础医学与临床

Objective To identify the potential association of transcription factor 7-like 2(TCF7L2 polymorphisms with type 2 diabetes mellitus in Uygur population of Xinjiang region .Methods In this case-control study ,819 ca-ses of type 2 diabetes mellitus patients were recruited in case group and 731 healthy individuals were selected as control.5 mL of blood sample were collected from each subject .The polymorphism was examined by matrix-assis-ted laser desorption/ionization-time of flight ( MALDI-TOF) and the OR value (95%CI) was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to type 2 diabetes mellitus and different geno-types.Results In case group, the frequencies of TC, CC genotype and C allele at rs7901695 were higher than the corresponding frequencies in control group (P<0.05).The interaction between TCF7L2 and environment risk factors did not contribute to the occurrence of the type 2 diabetes mellitus .Conclusions The polymorphisms of rs7091695 in TCF7L2 but not rs7085532 in TCG7L2 may be associated with type 2 diabetes mellitus in Uygur pop-ulation in Xinjiang region .

Non-Association between rs7903146 and rs12255372 Polymorphisms in Transcription Factor 7-Like 2 Gene and Type 2 Diabetes Mellitus in Jahrom City, Iran

BACKGROUND: Transcription factor 7-like 2 (TCF7L2) is a transcription factor in the Wnt signaling pathway. High levels of TCF7L2 have been reported in most human tissues, including the heart, lung, brain, liver, kidney, placenta, adipose tissues, and pancreatic beta-cells. The purpose of this study was to assess the association between TCF7L2 polymorphisms (rs12255372 and rs7903146) and type 2 diabetes mellitus in the city of Jahrom, Iran. METHODS: This case-control study was conducted with 200 patients referred to Diabetes Clinics and 200 healthy subjects in Jahrom City. Biochemical characteristics were first determined. TCF7L2 rs1255372 and rs7903146 polymorphisms were then genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: T-allele frequencies of both single nucleotide polymorphisms (SNPs) were significantly higher in diabetic patients than in normal glucose-tolerant subjects (rs12255372: 20.3% vs. 14.5%; rs7903146: 28.5% vs. 22.25%). The rs12255372 (G/T) polymorphism analysis showed an odds ratio of 0.473 (95% confidence interval [CI], 0.170 to 1.314; P=0.151) for the TT genotype and 0.646 (95% CI, 0.410 to 1.019; P=0.060) for the TG genotype, compared with the GG genotype. The rs7903146 (C/T) polymorphism odds ratios for TT and TC genotypes were 0.564 (95% CI, 0.280 to 1.135; P=0.109) and 0.751 (95% CI, 0.487 to 1.157; P=0.194) compared with the CC genotype, respectively. CONCLUSION: The rs12255372 and rs7903146 SNPs of the TCF7L2 gene were not associated with insulin resistance in the evaluated population.

Association of rs11196218, rs290487 polymorphisms in TCF7L2 gene with metabolic syndrome in type 2 diabetes mellitus population / 中国地方病学杂志

Objective To study the association of TCF7L2 gene rs11196218,rs290487 polymorphisms with metabolic syndrome in type 2 diabetes mellitus population.Methods According to the diagnostic criteria of international diabetes federation (IDF),680 cases of type 2 diabetes patients were divided into metabolic syndrome (MS) group and non metabolic syndrome (control) group.DNA was extracted from peripheral mononuclear cells,and then PCR was performed to specifically amplify TCF7L2 gene fragments.Gene polymorphisms were determined by connected enzyme detection reaction.After population representative was checked by Hardy-Weinberg equilibrium,statistical analysis was completed by software SPSS 13.0.Results The population was accorded with Hardy-Weinberg equilibrium and possessed the population representative.Frequency distributions of genotypes (GG,AG and AA) in TCF7L2 gene rs11196218 in MS and control groups were 55.6％(233/419),35.8％(150/419),8.6％ (36/419) and 54.8％ (126/230),39.1％ (90/230),6.1％ (14/230),respectively.Frequency distributions of alleles(G and A) in TCF7L2 gene rs11196218 in MS and control groups were 73.5％(616/838),26.5％(222/838)and 74.3％(342/460),25.7％(118/460),respectively.Frequency distributions of genotypes (GG,AG and AA) in TCF7L2 gene rs290487 in MS and control groups were 14.8％(62/418),42.3％(177/418),42.9％(179/418) and 15.0％(34/226),48.2％(109/226),36.8％(83/226),respectively.Frequency distributions of alleles(G and A) in TCF7L2 gene rs11196218 in MS and control groups were 36.0％ (301/836),64.0％ (535/836) and 39.1％ (177/452),60.9％ (275/452),respectively.Frequency distribution of allele and genotype in TCF7L2 genes rsl 1196218 and rs290487 between the two groups were not associated with metabolic syndrome in type 2 diabetes population (P ＞ 0.05).Conclusions TCF7L2 gene rs11196218,rs290487 polymorphisms has not association with metabolic syndrome of type 2 diabetes.

Association of the rs7903146 single nucleotide polymorphism at the Transcription Factor 7-like 2 (TCF7L2) locus with type 2 diabetes in Brazilian subjects / Associação do polimorfismo de nucleotídeo único rs7903146 no locus do TCF7L2 com diabetes tipo 2 em indivíduos brasileiros

OBJECTIVE:To investigate the association of the T allele of the single nucleotide polymorphism (SNP) rs7903146 of TCF7L2 with the occurrence of T2D in a sample of subjects followed up at the Brasilia University Hospital. SUBJECTS AND METHODS: The SNP rs7903146 of TCF7L2 was genotyped by allele-specific PCR in 113 patients with known T2D and in 139 non-diabetic controls in Brasilia, Brazil. RESULTS:We found that the T allele of the SNP rs7903146 of TCF7L2 was significantly associated with T2D risk (odds ratio of 3.92 for genotype TT in the recessive genetic model, p = 0.004 and 1.5 for T allele, p = 0.032). CONCLUSION:These results reinforce previous findings on the consistent association of this genetic factor and the risk of T2D in populations of diverse ethnic backgrounds. Arq Bras Endocrinol Metab. 2012;56(8):479-84.

OBJETIVO: Investigar a associação do alelo T do polimorfismo de nucleotídeo único (SNP) rs7903146 do TCF7L2 com a ocorrência de DM2 em uma amostra de indivíduos acompanhados no Hospital Universitário de Brasília. SUJEITOS E MÉTODOS: O SNP 7903146 do TCF7L2 foi genotipado por PCR alelo-específica em 113 pacientes portadores de DM2 e em 139 controles não diabéticos em Brasília, Brasil. RESULTADOS: Foi observada associação significativa do alelo T do SNP rs7903146 do TCF7L2 com a ocorrência de DM2 (razão de chances de 3,92 para o genótipo TT utilizando o modelo genético recessivo, p = 0,003; e de 1,5 para o alelo T, p = 0,032). CONCLUSÃO: Esse resultado reforça os achados prévios de associação consistente desse fator genético com o risco de diabetes em populações de origens étnicas diversas. Arq Bras Endocrinol Metab. 2012;56(8):479-84.

Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians.

Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 ( 201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population.

Variants of transcription factor 7-like 2 (TCF7L2) gene and incident glucose intolerance in Japanese-Brazilians

Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.

Association between polymorphisms of transcription factor 7-like 2 gene and type 2 diabetes mellitus in Hefei district / 中华内分泌代谢杂志

To explore the association between polymorphisms of transcription factor 7-like 2 gene (TCF7L2) and type 2 diabetes mellitus in Hefei district. The results suggest that the genetic variation DG10S478 in the TCF7L2 gene was not associated with type 2 diabetes mellitus in Hefei district ( P>0.05 ). However, its attribution to the susceptibility of type 2 diabetes mellitus in Hefei is not important.

Interactions of genes and diet in type 2 diabetes mellitus / 中华内分泌代谢杂志

The interactions between genetic variations and dietary factors in type 2 diabetes mellitus have attracted some attention. Several studies revealed that dietary carbohydrate quality and quantity and increased dietary fat intake might interact with genetic variations of type 2 diabetes mellitus and increase risk of this disease. Genome-wide association studies suggest that genetic variance may modulate the association between dietary pattern and type 2 diabetes mellitus.

Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population

The transcription factor 7-like 2 gene (TCF7L2) rs7903146 T allele is constantly associated with Type 2 diabetes in various populations and ethnic groups. Nevertheless, this has not been observed in two studies involving Arab populations. The aim of the present study was to investigate the association between TCF7L2 rs7903146 in an Iranian population. Type 2 diabetes patients (N = 258) and normal healthy control subjects (N = 168) from the same area, were examined. The ARMS-PCR (Amplification Refractory Mutation System) technique, subsequently validated by direct sequencing, was used for genotyping. Allele and genotype frequencies were significantly different between patients and controls TT vs. CT + CC [p 0.0081 OR 3.4 95 percentCI (1.27-11.9)] and T vs. C allele [p 0.02 OR 1.4 95 percentCI (1.03-1.9)]. Our data thus confirm the association between the rs7903146 T allele and T2D in an Iranian population, contrary to previous reports in Arab populations. This can possibly be attributed to differences in ethnic background or the effects of environmental factors.

Association of polymorphisms in transcription factor 7-like 2(TCF7L2) gene with type 2 diabetes in Chinese Han population / 中华内分泌代谢杂志

Objective To study the association of transcription factor 7-like 2(TCF7L2)polymorphisms with tvpe 2 diabetes mellitus in Chinese Han population. Methods Two polymorphisms (rs7903146 and rs12255372)of TCF7L2 gene were genotyped in 446 patients with type 2 diabetes mellitus(T2DM group)and 303 normal subiects (NC group) by PCR-restriction fragment length polymorphism(PCR-RFLP).Waist circumference.body mass index,plasma glucose,serum insulin,lipid profiles,high-sensitivity C-reactive protein and non-esterified fatty acid were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and β-cell function(HOMA-β)were calculated.Results (1) In T2DM group,T allele frequency and CT,TY geno tvpe frequeneies of rs7903146 were significantly higher than those in NC group(0.093,0.150,0.018 vs 0.043, 0.079,0.003,respectively,a11 P<O.O 1).Logistic regression analysis showed that the CT/TT genotype was a risk factor of tvpe 2 diabetes(OR=2.25,95%CI 1.39-3.62,P=0.001)and was associated with the decrease of insulin secretion. (2) No significant association was observed in vs12255372 alleles and genotypes with type 2 diabetes mellitus.Conclusion These results indicate that TCF7L2 might be one of the candidate genes for confe ring susceptibi lity to type 2 diabetes mellitus in the Chinese Han population.