Gene-gene interactions and the contribution of polymorphic loci of the KCNJ11, ADIPOQ, omentin, leptin, TCF7L2 and PPARg genes to the development of type 2 diabetes mellitus in the Kyrgyz population: a case-control genetic association study using MDR analysis

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There are many genetic loci associated with type 2 diabetes mellitus (T2DM). The genetic factors involved in the development of the T2DM can depend on the nature of genetic variation within and across different ethnic groups.

Aims — the aim of this study was to investigate the gene-gene interactions and to determine the role of the KCNJ11 (Glu23Lys), ADIPOQ (G276T), omentin (Val109Asp), leptin (G2548A), TCF7L2 (IVS3C/T), PPARg (Pro12Ala) genes in the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population using MDR analysis.

Material and methods. We examined 114 patients (53 females and 61 males; mean age, 54±7.4) with T2DM and 109 apparently healthy controls (48 females and 61 males; mean age, 50±8.4). Polymorphisms of the KCNJ11 (Glu23Lys), ADIPOQ (G276T), omentin (Val109Asp), leptin (G2548A), TCF7L2 (IVS3C/T), PPARg (Pro12Ala) genes were defined by PCR-RFLP assay.

Results. Among the six genes (KCNJ11, ADIPOQ, omentin, leptin, TCF7L2, PPARg) included in this study, the most significant contribution to the development of T2DM in the Kyrgyz population was detected for the ADIPOQ (2.17%) and KCNJ11 genes (2.01%).

The heterozygous genotype G276T (OR=1.79 CI 95% 1.05—3.05; p=0.036) and the 276T allele (OR=1.68 CI 95% 1.09—2.60; p=0.025) of the ADIPOQ gene were associated with a high risk of developing T2DM in the Kyrgyz population. The 23Lys allele of the KCNJ11 gene was significantly associated with T2DM in the Kyrgyz population (OR=1.62 CI 95% 1.10—2.38; p=0.019). The allele and genotype frequencies of the omentin (Val109Asp), leptin (G2548A), TCF7L2 (IVS3C/T), PPARg (Pro12Ala) genes did not differ between the studied groups (p>0.05).

Conclusions. In Kyrgyz population, the polymorphic loci Glu23Lys of the KCNJ11 gene, the 276T allele and genotype G276T of ADIPOQ are associated with T2DM. The omentin (Val109Asp), leptin (G2548A), TCF7L2 (IVS3C/T), and PPARg (Pro12Ala) genes alone do not have such a significant impact on the development of type 2 diabetes; they contribute to the phenotypic development of T2DM mainly due to gene-gene interactions.

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About the authors

Zhainagul T. Isakova

Research Institute of Molecular Biology and Medicine

Author for correspondence.
ORCID iD: 0000-0002-3681-6939
SPIN-code: 2489-8031


Kyrgyzstan, Bishkek

Elnura T. Talaibekova

Research Institute of Molecular Biology and Medicine

ORCID iD: 0000-0002-4619-1928
SPIN-code: 5722-1198
Kyrgyzstan, Bishkek

Baktygul Zh. Zhyrgalbekova

Research Institute of Molecular Biology and Medicine

ORCID iD: 0000-0003-0855-9450
SPIN-code: 6738-1297
Kyrgyzstan, Bishkek

Erkin M. Mirrakhimov

National Center of Cardiology and Internal Medicine

ORCID iD: 0000-0003-2982-6108

MD, PhD, Professor

Kyrgyzstan, Bishkek

Nazira M. Aldasheva

Research Institute of Molecular Biology and Medicine; Kyrgyz-Russian Slavic University

ORCID iD: 0000-0002-0356-9118
SPIN-code: 2633-7587


Kyrgyzstan, Bishkek

Almaz A. Aldashev

Research Institute of Molecular Biology and Medicine

ORCID iD: 0000-0002-4793-2206

MD, PhD, Professor

Kyrgyzstan, Bishkek


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Supplementary files

Supplementary Files
1. Сопроводительное письмо_2017_Бишкек

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2. Fig. 1. Electrophoregram of the Glu23Lys polymorphism of the KCNJ11 gene.

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3. Fig. 2. Electrophoregram of the G276T polymorphism of the ADIPOQ gene.

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4. Fig. 3. Electrophoregram of Val109Asp polymorphism of omentin gene.

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5. Fig. 4. Electrophoregram locus G2548A leptin gene.

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6. Fig. 5. Electrophoretic separation of genotypes of the IVS3C / T polymorphic locus of the TCF7L2 gene after restriction.

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7. Fig. 6. Electrophoretic separation of the genotypes of the polymorphic locus Pro12Ala PPARg gene after restriction.

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8. Fig. 7. Intergenic interactions of polymorphic loci of KCNJ11 (Glu23Lys) genes, ADIPOQ (G276T), romentina (Val109Asp), leptin (G2548A), TCF7L2 (IVS3C / T) and the PPARg (Pro12Ala) gene in the formation of predisposition SD2 in the Kyrgyz population. Red indicates a high degree of synergistic interaction, orange indicates a lower degree of interaction; brown the second is an intermediate stage between joint actions and antagonism (lack of communication or independence of the effects of individual loci); green and blue - antagonism of effects with lesser and greater degree.

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Abstract: 99

Remote (Russian): 46


Copyright (c) 2021 Isakova Z.T., Talaibekova E.T., Zhyrgalbekova B.Z., Mirrakhimov E.M., Aldasheva N.M., Aldashev A.A.

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