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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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Abstract


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.


Zhainagul T. Isakova

Research Institute of Molecular Biology and Medicine

Author for correspondence.
Email: jainagul@mail.ru
ORCID iD: 0000-0002-3681-6939
SPIN-code: 2489-8031

Kyrgyzstan, Bishkek

MD, PhD

Elnura T. Talaibekova

Research Institute of Molecular Biology and Medicine

Email: elya-1209@mail.ru
ORCID iD: 0000-0002-4619-1928
SPIN-code: 5722-1198

Kyrgyzstan, Bishkek

Baktygul Zh. Zhyrgalbekova

Research Institute of Molecular Biology and Medicine

Email: happyflower7@mail.ru
ORCID iD: 0000-0003-0855-9450
SPIN-code: 6738-1297

Kyrgyzstan, Bishkek

Erkin M. Mirrakhimov

National Center of Cardiology and Internal Medicine

Email: erkmirr@gmail.com
ORCID iD: 0000-0003-2982-6108

Kyrgyzstan, Bishkek

MD, PhD, Professor

Nazira M. Aldasheva

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

Email: aldashev@gmail.com
ORCID iD: 0000-0002-0356-9118
SPIN-code: 2633-7587

Kyrgyzstan, Bishkek

MD, PhD

Almaz A. Aldashev

Research Institute of Molecular Biology and Medicine

Email: aldashev@gmail.com
ORCID iD: 0000-0002-4793-2206

Kyrgyzstan, Bishkek

MD, PhD, Professor

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Supplementary files

Supplementary Files Action
1. Сопроводительное письмо_2017_Бишкек View (180KB) Indexing metadata
2. Fig. 1. Electrophoregram of the Glu23Lys polymorphism of the KCNJ11 gene. View (31KB) Indexing metadata
3. Fig. 2. Electrophoregram of the G276T polymorphism of the ADIPOQ gene. View (37KB) Indexing metadata
4. Fig. 3. Electrophoregram of Val109Asp polymorphism of omentin gene. View (39KB) Indexing metadata
5. Fig. 4. Electrophoregram locus G2548A leptin gene. View (32KB) Indexing metadata
6. Fig. 5. Electrophoretic separation of genotypes of the IVS3C / T polymorphic locus of the TCF7L2 gene after restriction. View (33KB) Indexing metadata
7. Fig. 6. Electrophoretic separation of the genotypes of the polymorphic locus Pro12Ala PPARg gene after restriction. View (35KB) Indexing metadata
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. View (1MB) Indexing metadata

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Copyright (c) 2018 Isakova Z.T., Talaibekova E.T., Zhyrgalbekova B.Z., Mirrakhimov E.M., Aldasheva N.M., Aldashev A.A.

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