Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms

Aim. To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. Subjects and methods. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. Results. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). Conclusion. The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically significantly associated with the development of T2DM; however, its predisposing effect has been identified in its combination with the variant genotypes of the polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

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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

Problems of Endocrinology ◽

10.14341/probl8344 ◽

2018 ◽

Vol 64 (4) ◽

pp. 216-225

Author(s):

Zhainagul T. Isakova ◽

Elnura T. Talaibekova ◽

Baktygul Zh. Zhyrgalbekova ◽

Erkin M. Mirrakhimov ◽

Nazira M. Aldasheva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Interactions ◽

Polymorphic Loci ◽

Adipoq Gene ◽

Genotype Frequencies ◽

Kcnj11 Gene ◽

Kyrgyz Population

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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PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor

Metabolism ◽

10.1016/j.metabol.2009.07.043 ◽

2010 ◽

Vol 59 (4) ◽

pp. 492-501 ◽

Cited By ~ 44

Author(s):

Dharambir Kaur Sanghera ◽

Fatma Yesim Demirci ◽

Latonya Been ◽

Lyda Ortega ◽

Sarju Ralhan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Asian Indian ◽

Gene Polymorphisms ◽

Adipoq Gene ◽

Diabetes Mellitus Risk

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Association of TCF7L2 gene polymorphisms with type 2 diabetes mellitus in Han Chinese population: A meta-analysis

Gene ◽

10.1016/j.gene.2012.09.034 ◽

2013 ◽

Vol 512 (1) ◽

pp. 76-81 ◽

Cited By ~ 6

Author(s):

Bu-Chun Zhang ◽

Wei-Ming Li ◽

Meng-Yun Zhu ◽

Ya-Wei Xu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Chinese Population ◽

Meta Analysis ◽

Han Chinese ◽

Tcf7l2 Gene ◽

Han Chinese Population

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Role of KCNJ11 Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

Pharmacologia ◽

10.5567/pharmacologia.2015.149.159 ◽

2015 ◽

Vol 6 (5) ◽

pp. 149-159

Author(s):

M. Aktaruzzam ◽

M.S. Islam ◽

M.M.R. Howlader ◽

M.M. Hossain ◽

M.SD. Islam

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Kcnj11 Gene

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Association of TCF7L2 gene polymorphisms with susceptibility to type 2 diabetes mellitus in a Chinese Hui population

Genetics and Molecular Research ◽

10.4238/2015.august.21.13 ◽

2015 ◽

Vol 14 (3) ◽

pp. 10064-10071 ◽

Cited By ~ 5

Author(s):

Y. Yang ◽

J.R. Xu ◽

Y.J. Wang ◽

X.M. Liu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Tcf7l2 Gene

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Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals

Molecular Biology Reports ◽

10.1007/s11033-011-0782-6 ◽

2011 ◽

Vol 39 (1) ◽

pp. 645-659 ◽

Cited By ~ 15

Author(s):

Lijuan Yang ◽

Xianghai Zhou ◽

Yingying Luo ◽

Xiuqin Sun ◽

Yong Tang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Meta Analysis ◽

East Asian ◽

Asian Populations ◽

Kcnj11 Gene

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Polymorphisms Glu23Lys of KCNJ11 gene are associated with Type 2 diabetes in the Kyrgyz Population

Problems of Endocrinology ◽

10.14341/probl201561526-29 ◽

2016 ◽

Vol 61 (5) ◽

pp. 26-29

Author(s):

Jainagul Tolonovna Isakova ◽

Elnura Talaybekovna Talaibekova ◽

Dinara Isfanbekovna Isabaeva ◽

Olga Sergeevna Lunegova ◽

Alina Suyuntbekovna Kerimkulova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Additive Models ◽

Homozygous Genotype ◽

Kcnj11 Gene ◽

Polymorphic Position ◽

Pcr Rflp ◽

Kyrgyz Population

Aim — in this study, we investigated whether polymorphisms Glu23Lys in KCNJ11 are associated with Type 2 diabetes mellitus (T2DM) in the Kyrgyz population.Material and methods. We genotyped 287 Kyrgyz individuals. A case—control study was performed, including 178 patients with T2DM (female — 55, male — 123, average age 54±6,6) and 109 non-diabetes controls (female — 48, male — 61, average age 50±8,4). The genotypes of polymorphic position Glu23Lys of KCNJ11 were determined by PCR-RFLP assay.Results. Genotypes Glu23Lys and Lys23Lys, containing the minor allele 23Lys, were more frequent in the group of type 2 diabetes (χ2=4,09; p=0,043). The allele 23Lys of KCNJ11 gene is associated with a high risk of developing type 2 diabetes in the Kyrgyz population [OR=1,46 (1,02—2,07); p=0,036]. Homozygous genotype Glu23Glu and allele Glu23 reduces the risk of developing type 2 diabetes [OR=0,61 (0,37—0,99); p=0,043 and OR=0,69 (0,48—0,98); p=0,037], respectively).Conclusion. Polymorphisms Glu23Lys of KCNJ11 gene are associated with the risk of Type 2 diabetes mellitus in the Kyrgyz Population according to the dominant and additive models of inheritance of the trait. Our results indicate that the allele 23Lys of KCNJ11 gene confers an elevated risk for the development of Type 2 diabetes mellitus in the Kyrgyz population.

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