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

1. Дедов И.И. Инновационные технологии в лечении и профилактике сахарного диабета и его осложнений. // Сахарный диабет. – 2013. – Т. 16. - №3 – С. 4–10. [Dedov II. Novel technologies for the treatment and prevention of diabetes mellitus and its complications. Diabetes Mellitus. 2013(3):4-10. (in Russ.)] doi: 10.14341/2072-0351-811.

2. Florez JC. The Genetics of Type 2 Diabetes: A Realistic Appraisal in 2008. The Journal of Clinical Endocrinology & Metabolism. 2008;93(12):4633-4642. doi: 10.1210/jc.2008-1345.

3. Lasram K, Ben Halim N, Hsouna S, et al. Evidence for Association of the E23K Variant ofKCNJ11Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis. BioMed Research International. 2014;2014:1-9. doi: 10.1155/2014/265274.

4. Devaney J, Qiu L, Na R, et al. Quantitative Assessment of the Effect of KCNJ11 Gene Polymorphism on the Risk of Type 2 Diabetes. PLoS One. 2014;9(4):e93961. doi: 10.1371/journal.pone.0093961.

5. Hani EH, Boutin P, Durand E, et al. Missense mutations in the pancreatic islet beta cell inwardly rectifying K + channel gene (KIR6.2/BIR ): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians. Diabetologia. 1998;41(12):1511-1515. doi: 10.1007/s001250051098.

6. Qin LJ, Lv Y, Huang QY. Meta-analysis of association of common variants in the KCNJ11-ABCC8 region with type 2 diabetes. Gen Mol Res. 2013;12(3):2990-3002. doi: 10.4238/2013.August.20.1.

7. Li Y-y. The KCNJ11 E23K gene polymorphism and type 2 diabetes mellitus in the Chinese Han population: a meta-analysis of 6,109 subjects. Mol Biol Rep. 2012;40(1):141-146. doi: 10.1007/s11033-012-2042-9.

8. Diagnosis and classification of diabetes mellitus. In: Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 1999. Part 1. 65 p.

9. Rabbani M, Sadeghi H, Moazen F, et al. Association of KCNJ11 (E23K) gene polymorphism with susceptibility to type 2 diabetes in Iranian patients. Advanced Biomedical Research. 2015;4(1):1. doi: 10.4103/2277-9175.148256.

10. Zhou D, Zhang D, Liu Y, et al. The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population. J Hum Genet. 2009;54(7):433-435. doi: 10.1038/jhg.2009.54.

11. Sakamoto Y, Inoue H, Keshavarz P, et al. SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population. J Hum Genet. 2007;52(10):781-793. doi: 10.1007/s10038-007-0190-x.

12. Koo BK, Cho YM, Park BL, et al. Polymorphisms ofKCNJ11(Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population. Diabet Med. 2007;24(2):178-186. doi: 10.1111/j.1464-5491.2006.02050.x.

13. Потапов В.А. Поиск генетических маркеров, определяющих предрасположенность к сахарному диабету 2 типа. Автореф. … канд. биол. наук. – M.; 2010. 24 c. [Potapov VA. Poisk geneticheskikh markerov, opredelyayushchikh predraspolozhennost' k sakharnomu diabetu 2 tipa [dissertation abstract]. Moscow; 2010. 24 p. (in Russ.)]

14. Gloyn AL, Weedon MN, Owen KR, et al. Large-Scale Association Studies of Variants in Genes Encoding the Pancreatic β-Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) Confirm That the KCNJ11 E23K Variant Is Associated With Type 2 Diabetes. Diabetes. 2003;52(2):568-572. doi: 10.2337/diabetes.52.2.568.

15. Ezzidi I, Mtiraoui N, Cauchi S, et al. Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study. BMC Med Genet. 2009;10(1):33. doi: 10.1186/1471-2350-10-33.

16. Jiang Y-D, Chuang L-M, Pei D, et al. Genetic Variations in the Kir6.2 Subunit(KCNJ11)of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan. Int J Endocrinol. 2014;2014:1-7. doi: 10.1155/2014/983016.