DISTRIBUTION OF 𝘒𝘊𝘕𝘑11 RS5219 POLYMORPHISM IN VIETNAMESE POPULATION AND ITS ASSOCIATION WITH HYPERGLYCEMIA

Thi Trung Thu NGUYEN1, Quang Binh TRAN2,
1 Department of BiologyHanoi National University of Education, Hanoi, Viet Nam
2 National Institute of Nutrition, Hanoi, Viet Nam

Main Article Content

Abstract

Aims: KCNJ11 gene, encoding ATP-sensitive channel subunits, involves in insulin secretion. The study aimed at investigating the distribution of the KCNJ11 E23K (rs5219) polymorphism and its association with prediabetes and type 2 diabetes (T2D) in Vietnamese population.


Methods: A cross-sectional study randomly recruited 2.676 participants aged 40-64 years from a general population in Ha Nam province, Vietnam. Glycemic status of the subjects was classified based on fasting plasma glucose and oral glucose tolerance test. PCR-restriction fragment length polymorphism method was applied to detect the KCNJ11-rs5219 polymorphism. Genotype frequencies were compared to find the distribution difference among normoglycemic, prediabetes, and T2D groups. Generalized linear models and multinomial logistic regression analysis were used to determine the associations of the KCNJ11-rs5219 polymorphism with prediabetes and T2D.


Results: The frequencies of minor K allele in normoglycemic, prediabetes and T2D groups were 33.2, 32.6 and 35.4%, respectively. Genotype distribution of the E23K polymorphism was in Hardy-Weinberg equilibrium and not significantly different among the three glucose groups (p > 0.05). Fasting plasma glucose and 2-h glucose levels were not significantly different among three genotypes EE, EK, and KK (p > 0.05). After adjusted for social-economic status, lifestyle and clinical patterns, no significant association was found between the KCNJ11-rs5219 polymorphism and hyperglycemia with ORs from 0.80 to 1.29.


Conclusions: The minor K allele was predominant and genotype frequency in the population was remained constant among generations. The study suggests no significant association between the KCNJ11-rs5219 polymorphism and hyperglycemia in the Vietnamese population.

Article Details

References

1. Federation ID. IDF diabetes altals 10th edition, 2021. https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf. Accessed May 9, 2022.
2. Ogurtsova K, da Rocha Fernandes J, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40-50.
3. Binh TQ, Phuong PT, Nhung BT, et al. Prevalence and correlates of hyperglycemia in a rural population, Vietnam: implications from a cross-sectional study. BMC Public Health. 2012;12(1): 939.
4. Billings LK, Florez JC. The genetics of type 2 diabetes: what have we learned from GWAS? Ann N Y Acad Sci. 2010;1212(1):59-77.
5. Cho YS, Chen C-H, Hu C, et al. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nature Genetics. 2012;44(1):67-72.
6. Miki T, Nagashima K, Seino S. The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J Mol Endocrinol. 1999; 22(2):113-123.
7. Sharma N, Crane A, Gonzalez G, et al. Familial hyperinsulinism and pancreatic β-cell ATP-sensitive potassium channels. Kidney International. 2000; 57(3): 803-808.
8. 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.
9. Nielsen E-MD, Hansen L, Carstensen B, et al. The E23K variant of Kir6. 2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes. 2003; 52(2):573-577.
10. 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. 2013;40(1):141-146.
11. Cheung CY, Tso AW, Cheung BM, et al. The KCNJ11 E23K polymorphism and progression of glycaemia in Southern Chinese: a long-term prospective study. PloS One 2011;6(12): e28598.
12. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2015; 38(Supplement 1): S8-S16.
13. Nguyen Thi Trung Thu and Tran Quang Binh. Determining KCNJ11 E23K polymorphism in a group of Vietnamese population by restriction fragment length polymorphism method. Journal of science: Chemical and Biological Science, Hanoi national university of Education 2016;61(9): 177-184.
14. Hansen SK, Nielsen E-MD, Ek J, et al. Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes. J Clin Endocrinol Metab. 2005;90(6):3629-3637.
15. Wang F, Han X-y, Ren Q, et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J. 2009;122(20):2477-2482.
16. Nikolac N, Simundic A-M, Katalinic D, et al. Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms. Arch Med Res. 2009;40(5):387-392.
17. Gloyn A, Hashim Y, Ashcroft S, et al. Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6. 2 with Type 2 diabetes mellitus (UKPDS 53). Diabetic Medicine. 2001;18(3):206-212.
18. Keshavarz P, Habibipour R, Ghasemi M, et al. Lack of genetic susceptibility of KCNJ11 E23K polymorphism with risk of type 2 diabetes in an Iranian population. Endocr Res. 2014;39(3):120-125.
19. 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.
20. Rizvi S, Raza ST, Mahdi F, et al. Genetic polymorphisms in KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) genes are associated with the risk of type 2 diabetes mellitus. Br J Biomed Sci. 2018:1-6.
21. Schwanstecher C, Schwanstecher M. Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes. Diabetes. 2002;51(suppl 3):S358-S362.
22. Koo B, Cho Y, Park B, et al. Polymorphisms of KCNJ11 (Kir6. 2 gene) are associated with Type 2 diabetes and hypertension in the Korean population. Diabetic Medicine. 2007; 24(2):178-186.
23. Čejková P, Novota P, Černá M, et al. KCNJ11 E23K polymorphism and diabetes mellitus with adult onset in Czech patients. Folia Biologica (Praha). 2007;53:173-175.
24. Lyssenko V, Almgren P, Anevski D, et al. Genetic prediction of future type 2 diabetes. PLoS Medicine. 2005;2(12): e345.
25. Abdelhamid I, Lasram K, Meiloud G, et al. E23K variant in KCNJ11 gene is associated with susceptibility to type 2 diabetes in the Mauritanian population. Prim Care Diabetes. 2014;8(2): 171-175.