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.

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.

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 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.

Allele-specific PCR assay to genotype SNP rs7903146 in TCF7L2 gene for rapid screening of diabetes susceptibility / Ensaio de PCR alelo-específico para genotipar o SNP rs7903146 no gene TCF7L2 para rápida triagem de suscetibilidade ao diabetes

OBJECTIVE: The aim of the present study is to validate a rapid and simple allele-specific PCR that genotypes TCF7/L2 rs7903146 (C/T) polymorphism with standard PCR instruments. METHODS: Two forward primers with variations in their 3' nucleotides were designed in such a way that each was specific for one of the two variants. They were combined with a common reverse primer into two PCR reactions. Specific amplification indicates the presence of the allele. One hundred and four DNA samples were genotyped by this method. To evaluate the assay, the polymorphism spanning region of 63 DNA samples representing the three possible genotypes was sequenced. RESULTS: The rs7903146 allele assignments derived from the allele-specific PCR were in complete agreement with sequencing. CONCLUSIONS: The assay described here is a suitable strategy for the TCF7/L2 rs7903146 (C/T) genotyping also allowing rapid and reliable identification.

OBJETIVO: O objetivo deste estudo foi validar um método de PCR alelo-específico, rápido e simples, para genotipagem do polimorfismo rs7903146 (C/T) no gene TCF7/L2 utilizando equipamentos convencionais. MÉTODOS: Dois primers forward com variações nos seus nucleotídeos 3' foram desenhados de forma que cada um fosse específico para uma das variantes. Eles foram combinados com um primer reverso comum em duas reações de PCR. A amplificação de tamanho específico indica a presença do alelo. Cento e quatro amostras de DNA foram genotipadas por esse método. Para validar o ensaio, uma amostragem representativa dos três possíveis genótipos (63 amostras) teve a região contendo o polimorfismo seqüenciada. RESULTADOS: A genotipagem do polimorfismo rs7903146 derivada da PCR alelo-específica estava em completa concordância com o sequenciamento. CONCLUSÕES: O ensaio aqui descrito é uma estratégia adequada para a genotipagem do polimorfismo rs7903146 (C/T) do gene TCF7/L2 e permite identificação alélica rápida e precisa.