Research of association of the polymorphic locus rs11212617 ATM gene with the response to therapy with metformin in patients with type 2 diabetes

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Abstract


Rationale. The genetic aspects influencing the effectiveness of metformin (MF) therapy in patients with type 2 diabetes mellitus (DMT2) have recently been intensively studied.

Objective — to study the association between the rs11212617 polymorphism in the ATM gene and response to metformin therapy in DMT2 patients in the Novosibirsk region and to conduct a metaanalysis of the previously reported data.

Material and methods. 460 DMT2 patients (97 males and 363 females) who received MF, both as a part of monotherapy and in combination with sulfonylurea (SU) drugs, were subjected to cross-sectional examination. Depending on HbA1c level, patients were divided into the following groups: patients who have attained the target HbA1c level after MF therapy (n=209) and those who did not attain the target HbA1c level although receiving the maximum dose of MF (n=251). Alleles and genotypes were determined by real-time PCR using TaqMan probes at the Institute of Chemical Biology and Fundamental Medicine (SB RAS).

Results. Frequency of the rare C allele of the rs11212617 polymorphism in the ATM gene in the examined patients was 0.41 and statistically did not differ between the subgroups who received MF monotherapy and combination therapy. Statistically significant association between the genotype of the rs11212617 polymorphism in the ATM gene and the type of response was revealed neither in the total group of patients (OR=0.94, 95% CI 0.73—1.23; p=0.67) nor in the MF monotherapy (OR=0.94, 95% CI 0.73—1.23; p=0.67) or combination therapy subgroups (OR=1.02, 95% CI 0.72—1.43; p=0.92). However, the metaanalysis results verify that the C allele is associated with attainment of the target HbAc1 level (the total OR=1.27, 95% CI 1.10—1.46; p=0.0008).

Conclusions. The rs11212617 polymorphism in the ATM gene can influence the effectiveness of MF therapy in DMT2 patients.


Irina A. Bondar

bondaria@oblmed.nsk.ru
ORCID iD: 0000-0003-4324-2926
SPIN-code: 6633-8947
Novosibirsk State Medical University
Russian Federation, 52 Krasny Prospect, Novosibirsk, 630091

MD, PhD, Professor

Olesia Y. Shabelnikova

Author for correspondence.
oushab@ngs.ru
ORCID iD: 0000-0003-3906-4784
SPIN-code: 5941-4815
Novosibirsk State Medical University; Novosibirsk State Regional Clinical Hospital
Russian Federation, 52 Krasny Prospect, Novosibirsk, 630091

MD, PhD

Ekaterina A. Sokolova

sokolovaea2608@gmail.com
ORCID iD: 0000-0003-2652-6644
SPIN-code: 2414-1230
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University
Russian Federation, 8 Lavrentiev Avenue, Novosibirsk, 630090; 52 Krasny Prospect, Novosibirsk, 630091

PhD

Maksim L. Filipenko

mlfilipenko@gmail.com
ORCID iD: 0000-0002-8950-5368
SPIN-code: 4025-0533
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University
Russian Federation, 8 Lavrentiev Avenue, Novosibirsk, 630090; 52 Krasny Prospect, Novosibirsk, 630091

PhD

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Copyright (c) Bondar I.A., Shabelnikova O.Y., Sokolova E.A., Filipenko M.L.

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