The role and interaction of polymorphic variants of non-allelic genes KCNJ11, ADIPOQ, ITLN1, LEP, TCF7L2, PPARG in the increase in the risk of diabetes type 2 in Kyrgyz Republic


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Abstract

Aim. To study the intergenic interaction and estimate the contribution of polymorphic loci p.K23E (rs5219, KCNJ11), g.15661G>T (rs1501299, ADIPOQ), p.V109D (rs2274907, ITLN1), g.2453G>A (rs7799039, LEP), g.53341C>T (rs7903146, TCF7L2), and p.P12A (rs1801282, PPARG) in the gain of the risk of DM2 using bioinformatics method of multifactor dimensionality reduction (MDR). Material and methods. A study conducted by the «case-control», included 114 patients (61 male (53,5%), 53 females (46,5%)) with DM2 (main group) and 109 patients (61 male (56%), 48 females (44%)) without DM2 (control group). Genotyping was performed by the PCR-RFLP. Analysis of intergenic interactions bioinformatics was conducted by the method of multifactor dimensionality reduction (Multifactor Dimensionality Reduction, MDR). Results. Among studied polymorphic variants the largest contribution to the gain in the risk of DM2 in persons of Kyrgyz nationality is contributee by g.15661G>T (ADIPOQ), and p.K23E (KCNJ11). Genetic markers of the elevated risk of DM2 include: allele T (OR=1,68; 95% CI=[1,09-2,60], p=0,025), the heterozygous genotype GT (OR=1,79, 95% CI=[1,05-3,05], p=0,037) of the polymorphism g.15661G>T (ADIPOQ), and allele A of the polymorphism p.K23E (KCNJ11) - OR=1,62 (95% CI=[1,10-2,38], p=0,019). Polymorphic loci p.V109D (ITLN1), g.2453G>A (LEP), g.53341C>T (TCF7L2) and p.P12A (PPARG) in the progress of DM2 do not have a significant impact individually, but the implementation in phenotypic DM2 they can take place due to the effect of intergenic interactions. In the presence of a genetic profile «CC (g.53341C>T, TCF7L2) / AG (g.2453G>A, LEP) / AA (p.K23E, KCNJ11)» and «CT (g.5341C>T, TCF7L2) / AA (g.2453G>A, LEP) / AG (p.K23E, KCNJ11)» the risk of developing DM2 increases by 5-8 times. Conclusion. For persons of Kyrgyz nationality polymorphic loci p.K23E (KCNJ11) and g.15661G>T (ADIPOQ) are associated with the increased risk of DM2. The loci g.2453G>A (LEP), p.V109D (ITLN1), g.53341C>T (TCF7L2) and p.P12A (PPARG) can affect the phenotypic realization of DM2 in combination with pathogenetically significant genotypes of the genes KCNJ11 and ADIPOQ.

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About the authors

Zh. T Isakova

Research Institute of Molecular Biology and Medicine

Email: jainagul@mail.ru
Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

V. N Kipen

The Institute of Genetics and Cytology of The National Academy of Sciences of Belarus

Email: jainagul@mail.ru
Akademicheskaya str, 27, Minsk, 220072, Republic of Belarus

E. T Talaibekova

Research Institute of Molecular Biology and Medicine

Email: jainagul@mail.ru
Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

A. A Aldashev

Research Institute of Molecular Biology and Medicine

Email: jainagul@mail.ru
Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

N. M Aldasheva

Research Institute of Molecular Biology and Medicine

Email: jainagul@mail.ru
Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

T. M Bectursunov

I.K. Akhunbaev Kyrgyz State Medical Academy

Email: jainagul@mail.ru
Akhunbaev str, 92, Bishkek, 720020, Kyrgyz Republic

E. M Mirrakhimov

National Center of Cardiology and Internal Medicine

Email: jainagul@mail.ru
Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

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