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Assessment of diabete treatment of individuals with diabetes type 2, with GLP-1 mimetic, exenatide, response to GLP1 mimetic of GLP-1 treatment, in patients with type 2 diabetes, related to the SNPs rs12255372 (G / T) and rs7903146 (C / T) of TCF7L2 gene

Grant number: 10/17943-7
Support type:Regular Research Grants
Duration: July 01, 2011 - June 30, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Rosa Ferreira dos Santos
Grantee:Rosa Ferreira dos Santos
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Screening for genetic polymorphisms in various populations, said the gene transcription factor TCF7L2 (Transcription Factor 7-Like 2), which has a significant association with T2DM. The TCF7L2 is a potent insulin secretagogue. It was observed that polymorphic variants present in the TCF7L2 gene may result in reduced insulin secretion stimulated by the action of GLP-1 secretion. The incretin effect, had been hampered in carrying the T allele of SNPs rs7903146 and rs 12,255,372 of that gene. These data suggest that in individuals carriers of these variants, the cell b respond less to GLP-1. The treatment of type 2 diabetes with exenatide, an analogue of GLP-1 in subjects with and those without the variants of the polymorphic SNPs rs7903146 (C / T) rs12255372 (G / T) is to evaluate the differences in the response. The indication of incretins to treat type 2 diabetes is aimed at promoting glycemic control through physiological mechanisms, reducing the risk of hypoglycemia and increasing the possibility of better control of postprandial glucose. Moreover, it is a chance to promote increased survival of beta cells. However, some studies have shown that the presence of polymorphic variants of the TCF7L2 gene, determine a reduction in secretion and sensitivity to GLP-1, suggesting that patients with these variants could not be good Responsoris to treatment with GLP-1 or its analogues . The purpose of this study is to evaluate the response to treatment with an agonist of GLP-1 (Exenatide) in subjects with DM2 and carriers of the variant polymorphic SNPs rs7903146 (C / T) and rs12255372 (G / T) of TCF7L2 assessing the relevance this polymorphism in the pattern of drug response. Be genotyped 300 type 2 diabetic patients using Real Time PCR quality, these will be held to select 30 individuals homozygous for the risk allele and 30 without the risk allele for both SNPs. The 2 groups will be treated with exenatide for 2 months and assessed before and after treatment compared to standard biochemical and hormonal. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA, MARI CASSOL; ROSSI DA SILVA, MARIA ELIZABETH; FUKUI, ROSA TSUNESHIRO; ARRUDA-MARQUES, MARIA DO CARMO; AZHAR, SALMAN; DOS SANTOS, ROSA FERREIRA. Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes. DIABETOLOGY & METABOLIC SYNDROME, v. 11, JAN 25 2019. Web of Science Citations: 1.
FERREIRA, MARI CASSOL; ROSSI DA SILVA, MARIA ELIZABETH; FUKUI, ROSA TSUNESHIRO; ARRUDA-MARQUES, MARIA DO CARMO; DOS SANTOS, ROSA FERREIRA. TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity. DIABETOLOGY & METABOLIC SYNDROME, v. 10, APR 26 2018. Web of Science Citations: 2.

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