Pharmacogenetic Aspects of Type 2 Diabetes Treatment
In this article, we analyze the role of different variants of the KCNJ11, TCF7L2, SLC22A1, SLC22A3, CYP2C9, CYP2C8, PPARγ genes polymorphisms in efficacy of diabetes mellitus pharmacotherapy. T allele of the KCNJ11 rs2285676 gene polymorphism and G allele of KCNJ11 rs5218 gene polymorphism are assoc...
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Scientific Сentre for Family Health and Human Reproduction Problems
2020
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oai:doaj.org-article:90bffad3c345457fba2a041e4979c0cf2021-11-23T06:14:44ZPharmacogenetic Aspects of Type 2 Diabetes Treatment2541-94202587-959610.29413/ABS.2020-5.3.2https://doaj.org/article/90bffad3c345457fba2a041e4979c0cf2020-07-01T00:00:00Zhttps://www.actabiomedica.ru/jour/article/view/2362https://doaj.org/toc/2541-9420https://doaj.org/toc/2587-9596In this article, we analyze the role of different variants of the KCNJ11, TCF7L2, SLC22A1, SLC22A3, CYP2C9, CYP2C8, PPARγ genes polymorphisms in efficacy of diabetes mellitus pharmacotherapy. T allele of the KCNJ11 rs2285676 gene polymorphism and G allele of KCNJ11 rs5218 gene polymorphism are associated with the response to IDPP-4 therapy; the presence of KCNJ11 gene rs5210 polymorphism A allele is a predictor of poor response. The effect of rs7903146 polymorphism of TCF7L2 gene was evaluated on the response to treatment of patients taking linagliptin. Linagliptin significantly reduced HbA1c levels for all three rs7903146 genotypes (CC: –0.82 %; CT: –0.77 %; TT: –0.57 %). A significantly smaller effect of therapy was observed with the genotype with ТТ. The rs622342 polymorphism of SLC22A1 gene was studied in effectiveness of metformin. The researches demonstrated that carriers of variant AA had an average decrease of HbA1c of 0.53 %, heterozygous – decrease of 0.32 %, and carriers of a minor variant of SS had an increase of 0.2 % in the level of HbA1c. A significant effect of CYP2C9 polymorphisms on the pharmacokinetic parameters of PSM was noted. When studying the kinetics of glibenclamide, it was found that carriage of the allele *2 significantly reduces glibenclamide metabolism: homozygous carriers had clearance 90 % lower than homozygous carriers of the wild variant. The studies confirmed the association of the allelic variants of Thr394Thr and Gly482Ser of PPARγ gene with higher efficacy of the rosiglitazone. The data obtained from the analysis of the association of the Pro12Ala polymorphism of PPARγ gene and the response to therapy is contradictory. Thus the personalized approach, based on the knowledge of polymorphism options, will allow choosing the most effective drug with transparent kinetics for each individual patient.N. O. PozdnyakovI. N. KagarmanyanA. E. MiroshnikovE. S. EmelyanovA. A. GruzdevaA. M. SirotkinaI. A. DukhaninaA. A. MilkinaA. A. KhokhlovS. O. PozdnyakovScientific Сentre for Family Health and Human Reproduction Problemsarticlediabetes mellituspharmacogeneticskcnj11tcf7l2slc22a1slc22a3cyp2c9cyp2c8pparγScienceQRUActa Biomedica Scientifica, Vol 5, Iss 3, Pp 13-23 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
RU |
| topic |
diabetes mellitus pharmacogenetics kcnj11 tcf7l2 slc22a1 slc22a3 cyp2c9 cyp2c8 pparγ Science Q |
| spellingShingle |
diabetes mellitus pharmacogenetics kcnj11 tcf7l2 slc22a1 slc22a3 cyp2c9 cyp2c8 pparγ Science Q N. O. Pozdnyakov I. N. Kagarmanyan A. E. Miroshnikov E. S. Emelyanov A. A. Gruzdeva A. M. Sirotkina I. A. Dukhanina A. A. Milkina A. A. Khokhlov S. O. Pozdnyakov Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| description |
In this article, we analyze the role of different variants of the KCNJ11, TCF7L2, SLC22A1, SLC22A3, CYP2C9, CYP2C8, PPARγ genes polymorphisms in efficacy of diabetes mellitus pharmacotherapy. T allele of the KCNJ11 rs2285676 gene polymorphism and G allele of KCNJ11 rs5218 gene polymorphism are associated with the response to IDPP-4 therapy; the presence of KCNJ11 gene rs5210 polymorphism A allele is a predictor of poor response. The effect of rs7903146 polymorphism of TCF7L2 gene was evaluated on the response to treatment of patients taking linagliptin. Linagliptin significantly reduced HbA1c levels for all three rs7903146 genotypes (CC: –0.82 %; CT: –0.77 %; TT: –0.57 %). A significantly smaller effect of therapy was observed with the genotype with ТТ. The rs622342 polymorphism of SLC22A1 gene was studied in effectiveness of metformin. The researches demonstrated that carriers of variant AA had an average decrease of HbA1c of 0.53 %, heterozygous – decrease of 0.32 %, and carriers of a minor variant of SS had an increase of 0.2 % in the level of HbA1c. A significant effect of CYP2C9 polymorphisms on the pharmacokinetic parameters of PSM was noted. When studying the kinetics of glibenclamide, it was found that carriage of the allele *2 significantly reduces glibenclamide metabolism: homozygous carriers had clearance 90 % lower than homozygous carriers of the wild variant. The studies confirmed the association of the allelic variants of Thr394Thr and Gly482Ser of PPARγ gene with higher efficacy of the rosiglitazone. The data obtained from the analysis of the association of the Pro12Ala polymorphism of PPARγ gene and the response to therapy is contradictory. Thus the personalized approach, based on the knowledge of polymorphism options, will allow choosing the most effective drug with transparent kinetics for each individual patient. |
| format |
article |
| author |
N. O. Pozdnyakov I. N. Kagarmanyan A. E. Miroshnikov E. S. Emelyanov A. A. Gruzdeva A. M. Sirotkina I. A. Dukhanina A. A. Milkina A. A. Khokhlov S. O. Pozdnyakov |
| author_facet |
N. O. Pozdnyakov I. N. Kagarmanyan A. E. Miroshnikov E. S. Emelyanov A. A. Gruzdeva A. M. Sirotkina I. A. Dukhanina A. A. Milkina A. A. Khokhlov S. O. Pozdnyakov |
| author_sort |
N. O. Pozdnyakov |
| title |
Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| title_short |
Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| title_full |
Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| title_fullStr |
Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| title_full_unstemmed |
Pharmacogenetic Aspects of Type 2 Diabetes Treatment |
| title_sort |
pharmacogenetic aspects of type 2 diabetes treatment |
| publisher |
Scientific Сentre for Family Health and Human Reproduction Problems |
| publishDate |
2020 |
| url |
https://doaj.org/article/90bffad3c345457fba2a041e4979c0cf |
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