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 УЧРЕДИТЕЛИ:
Институт теоретической и экспериментальной биофизики Российской академии наук.

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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 19, Art. 55 (pp. 743-756)    |    2018       
»

Influence of RS7903146 TCF7L2 polymorphism on the therspeutic response to gliclazide in patients with type 2 diabetes mellitus
Shorokhova P.B., Zagorodnikova K.A., Baranov V.L., Vorokhobina N.V., Murzina A.A., Abulula M., Dobrovolskaya L.M.

S.M. Kirov Military Medical Academy, Saint Petersburg, Russia



Brief summary

The rs7903146 polymorphism of TCF gene could affect insulin secretion stimulated by sulfonylurea (SU). As a result, interindividual variability of the pharmacological effect of gliclazide can be observed in patients carrying mutations of this gene. The aim of the study was to evaluate the influence of TCF7L2 polymorphism on the therapeutic response to gliclazide in patient with newly diagnosed type 2 diabetes mellitus (T2DM). Materials and methods. 68 patients with newly diagnosed diabetes and without overweight or obesity were examined. In all participants the main indicators of glycemic control were studied over 6 months of treatment with gliclazide; presence of rs7903146 TCF7L2 polymorphism was also determined. If necessary, dose titration was carried out or other glucose-lowering therapy (a combination of drugs or insulin) was prescribed. Results.The frequency of minor allele T in the study group was 0,26. The distributionof genotypes correspondedto the Hardy - Weinberg equation. According to the results of the study, among patients on monotherapy with gliclazide MB, after 6 months of observation, the target level of glycated hemoglobin reached 96,2% of patients (25 out of 26) with the CC-genotype rs7903146 of the TCF7L2 gene, among carriers of T risk allele (CT- and TT-genotypes) the percentage of patients who reached the target level of glycated hemoglobin was significantly less: 72% (18 out of 25);p=0.024 Conclusion: The presence of polymorphism rs7903146 in the TCF7L2 gene is associated with poor therapeutic response to gliclazide monotherapy in patients with T2DM.


Key words

diabetes mellitus, pharmacogenetics, polymorphism, sulphonylureas, gliklazide, rs7903146, TCF7L2





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