Investigating the rs2237892 and rs231362 Polymorphisms of KCNQ1 Gene Associations with Type 2 Diabetes in an Iranian Population 
(Yazd Province)

Padidaran, Mona; Mirzaei, Masoud; Shamsi, Farimah; Kalantar, Seyed Mehdi; Sheikhha, Mohammad Hasan

doi:10.18502/ijdo.v13i4.8000

Volume 13, Issue 4 (12-2021) IJDO 2021, 13(4): 215-223 | Back to browse issues page

‎ 10.18502/ijdo.v13i4.8000

Mendeley

Zotero

RefWorks

Padidaran M, Mirzaei M, Shamsi F, Kalantar S M, Sheikhha M H. Investigating the rs2237892 and rs231362 Polymorphisms of KCNQ1 Gene Associations with Type 2 Diabetes in an Iranian Population (Yazd Province). IJDO 2021; 13 (4) :215-223
URL: http://ijdo.ssu.ac.ir/article-1-666-en.html

Investigating the rs2237892 and rs231362 Polymorphisms of KCNQ1 Gene Associations with Type 2 Diabetes in an Iranian Population (Yazd Province)

Mona Padidaran

, Masoud Mirzaei

, Farimah Shamsi

, Seyed Mehdi Kalantar

, Mohammad Hasan Sheikhha ^*

Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract: (1103 Views)

Objective: Type 2 diabetes (T2DM) is a worldwide prevalent metabolic disorder and the cause of many morbidities and mortalities. KCNQ1 gene encodes α-subunit of voltage-gated potassium (K+) channel which plays a role in insulin secretion in the pancreas, thus its variants may confer susceptibility to diabetes. Recognition of genetic variants involved in T2DM could help the early diagnosis and prevention of the disease. The main purpose of this paper was to investigate the frequencies of rs231362 and rs2237892 polymorphisms of KCNQ1 gene in T2DM patients and comparing these frequencies with normal subjects in an Iranian population from Yazd province, Iran.
Materials and Methods: This case-control study was conducted on 166 patients with T2DM and 168 normal subjects. After obtaining the informed consent, 5 ml peripheral blood was taken from the cases and controls and then DNA was extracted. The molecular investigation was done using 4-primer ARMS PCR and PCR-RFLP methods.
Results: Statistical analysis showed that GG genotype [OR= 3.9 (2.1-7.1), P-value< 0.001] and G allele [OR=2.85 (2.07-3.93), P-value< 0.001] frequency of rs231362 polymorphism was significantly different between case and control groups. While rs2237892 polymorphism did not show any differences between the two groups.
Conclusion: The result of this study showed that GG genotype and G allele of rs231362 polymorphism can be related to T2DM susceptibility in the population under study.

Keywords: Type 2 diabetes, KCNQ1, Polymorphism, ARMS PCR, PCR-RFLP

Full-Text [PDF 726 kb] (409 Downloads)

Type of Study: Research | Subject: Special
Received: 2021/07/25 | Accepted: 2021/10/2 | Published: 2021/11/1

References

1. Ashcroft FM, Rorsman P. Diabetes mellitus and the β cell: the last ten years. Cell. 2012;148(6):1160-71. [DOI:10.1016/j.cell.2012.02.010]

2. Association AD. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(1):S14-S31. https://doi.org/10.2337/dc20-S002 [DOI:10.2337/dc20-S002.]

3. Giorgino F, Laviola L, Leonardini A. Pathophysiology of type 2 diabetes: rationale for different oral antidiabetic treatment strategies. Diabetes research and Clinical practice. 2005;68:S22-9. [DOI:10.1016/j.diabres.2005.03.012]

4. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. The Lancet. 2011;378(9786):169-81. [DOI:10.1016/S0140-6736(11)60614-4]

5. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes research and clinical practice. 2017;128:40-50. [DOI:10.1016/j.diabres.2017.03.024]

6. International Diabetes Federation. IDF Diabetes Atlas, 8th edn. Brussels, Belgium:International Diabetes Federation, 2017.

7. Lotfi MH, Saadati H, Afzali M. Prevalence of diabetes in people aged≥ 30 years: the results of screen-ing program of Yazd Province, Iran, in 2012. Journal of research in health sciences. 2013;14(1):88-92.

8. Haghdoost AA, Rezazadeh-Kermani M, Sadghirad B, Baradaran HR. Prevalence of type 2 diabetes in the Islamic Republic of Iran: systematic review and meta-analysis. 2009. [DOI:10.26719/2009.15.3.591]

9. Farshchi A, Esteghamati A, Sari AA, Kebriaeezadeh A, Abdollahi M, Dorkoosh FA, et al. The cost of diabetes chronic complications among Iranian people with type 2 diabetes mellitus. Journal of Diabetes & Metabolic Disorders. 2014;13(1):1-4. [DOI:10.1186/2251-6581-13-42]

10. Sunita Singh. The genetics of type 2 diabetes mellitus: a review. Journal of Scientific Research. 2011;55:35-48.

11. Sanghera DK, Blackett PR. Type 2 diabetes genetics: beyond GWAS. Journal of diabetes & metabolism. 2012;3(198). [DOI:10.4172/2155-6156.1000198]

12. Wolfs MG, Hofker MH, Wijmenga C, Van Haeften TW. Type 2 diabetes mellitus: new genetic insights will lead to new therapeutics. Current genomics. 2009;10(2):110-8. [DOI:10.2174/138920209787847023]

13. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature genetics. 2010;42(7):579-89. [DOI:10.1038/ng.609]

14. Tan JT, Nurbaya S, Gardner D, Ye S, Tai ES, Ng DP. Genetic Variation in KCNQ1 Associates With Fasting Glucose andβ-Cell Function: A Study of 3,734 Subjects Comprising Three Ethnicities Living in Singapore. Diabetes. 2009;58(6):1445-9. [DOI:10.2337/db08-1138]

15. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H,et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nature genetics. 2008;40(9):1092-7. [DOI:10.1038/ng.207]

16. Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature genetics. 2008;40(9):1098-102. [DOI:10.1038/ng.208]

17. Hara K, Shojima N, Hosoe J, Kadowaki T. Genetic architecture of type 2 diabetes. Biochemical and biophysical research communications. 2014 ;452(2):213-20. [DOI:10.1016/j.bbrc.2014.08.012]

18. Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. European journal of clinical investigation. 2011;41(6):679-92. [DOI:10.1111/j.1365-2362.2010.02454.x]

19. Jespersen T, Grunnet M, Olesen SP. The KCNQ1 potassium channel: from gene to physiological function. Physiology. 2005;20(6):408-16. [DOI:10.1152/physiol.00031.2005]

20. Warth R, Alzamora MG, Kim J, Zdebik A, Nitschke R, Bleich M, et al. The role of KCNQ1/KCNE1 K+ channels in intestine and pancreas: lessons from the KCNE1 knockout mouse. Pflügers Archiv. 2002;443(5):822-8. [DOI:10.1007/s00424-001-0751-3]

21. ncbi. KCNQ1 potassium voltage-gated channel subfamily Q member 1 [ Homo sapiens (human) ]. 2018.

22. McCarthy MIJNEJoM. Genomics, type 2 diabetes, and obesity. 2010;363(24):2339-50. [DOI:10.1056/NEJMra0906948]

23. Yazdi KV, Kalantar SM, Houshmand M, Rahmanian M, Manaviat MR, Jahani MR, et al. SLC30A8, CDKAL1, TCF7L2, KCNQ1 and IGF2BP2 are associated with type 2 diabetes mellitus in Iranian patients. Diabetes, metabolic syndrome and obesity: targets and therapy. 2020;13:897. [DOI:10.2147/DMSO.S225968]

24. Erfani T, Sarhangi N, Afshari M, Abbasi D, Meybodi HR, Hasanzad M. KCNQ1 common genetic variant and type 2 diabetes mellitus risk. Journal of Diabetes & Metabolic Disorders. 2020;19(1):47-51. [DOI:10.1007/s40200-019-00473-4]

25. Baniasadian S, Farajnia S, Jafari B. Frequency of KCNQ1 variant rs2237892 in type 2 diabetes in East Azerbaijan population, northwest of Iran. Acta Medica Iranica. 2018:90-4.

26. Been LF, Ralhan S, Wander GS, Mehra NK, Singh J, Mulvihill JJ, et al. Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US. BMC medical genetics. 2011;12(1):1-0. [DOI:10.1186/1471-2350-12-18]

27. Rees SD, Hydrie MZ, Shera AS, Kumar S, O'Hare JP, Barnett AH, et al. Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations. Diabetologia. 2011;54(6):1368-74. [DOI:10.1007/s00125-011-2063-2]

28. Al‐Daghri NM, Alkharfy KM, Alokail MS, Alenad AM, Al‐Attas OS, Mohammed AK, et al. Assessing the contribution of 38 genetic loci to the risk of type 2 diabetes in the S audi A rabian P opulation. Clinical endocrinology. 2014;80(4):532-7. [DOI:10.1111/cen.12187]

29. Lu S, Xie Y, Lin K, Li S, Zhou Y, Ma P, et al. Genome-wide association studies-derived susceptibility loci in type 2 diabetes: confirmation in a Chinese population. Clinical and Investigative Medicine. 2012:E327-33. [DOI:10.25011/cim.v35i5.18706]

30. Ohshige T, Iwata M, Omori S, Tanaka Y, Hirose H, Kaku K, et al. Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. PloS one. 2011;6(10):e26911. [DOI:10.1371/journal.pone.0026911]

31. Ng MC, Saxena R, Li J, Palmer ND, Dimitrov L, Xu J, et al. Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. Diabetes. 2013;62(3):965-76. [DOI:10.2337/db12-0266]

32. Long J, Edwards T, Signorello LB, Cai Q, Zheng W, Shu XO, et al. Evaluation of genome-wide association study-identified type 2 diabetes loci in African Americans. American journal of epidemiology. 2012;176(11):995-1001. [DOI:10.1093/aje/kws176]

33. Hu C, Wang C, Zhang R, Ma X, Wang J, Lu J, et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009;52(7):1322-5. [DOI:10.1007/s00125-009-1335-6]

34. Lin YD, Qian Y, Dong MH, Lu F, Shen C, Jin GF, et al. Association of polymorphisms of potassium voltage-gated channel, KQT-like subfamily, member 1 and type 2 diabetes in Jiangsu province, China. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. 2013;47(6):538-41.

35. Park SE, Lee WY, Oh KW, Baek KH, Yoon KH, Kang MI,et al. Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea. Journal of human genetics. 2012;57(4):265-8. [DOI:10.1038/jhg.2012.16]

36. Saif-Ali R, Muniandy S, Al-Hamodi Z, Lee CS, Ahmed KA, Al-Mekhlafi AM, et al. KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects. Annals of the Academy of Medicine-Singapore. 2011;40(11):488. [DOI:10.3390/ijms12095705]

37. Turki A, Mtiraoui N, Al-Busaidi AS, Khirallah M, Mahjoub T, Almawi WY. Lack of association between genetic polymorphisms within KCNQ1 locus and type 2 diabetes in Tunisian Arabs. Diabetes research and clinical practice. 2012;98(3):452-8. [DOI:10.1016/j.diabres.2012.10.006]

38. Almawi WY, Nemr R, Keleshian SH, Echtay A, Saldanha FL, AlDoseri FA, et al. A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population. Diabetes research and clinical practice. 2013;102(2):117-22. [DOI:10.1016/j.diabres.2013.09.001]

39. van Vliet-Ostaptchouk JV, van Haeften TW, Landman GW, Reiling E, Kleefstra N, Bilo HJ, et al. Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp. PloS one. 2012;7(3):e32148. [DOI:10.1371/journal.pone.0032148]

40. Gamboa-Melendez MA, Huerta-Chagoya A, Moreno-Macías H, Vazquez-Cardenas P, Ordonez-Sanchez ML, Rodriguez-Guillen R, et al. Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population. Diabetes. 2012;61(12):3314-21. [DOI:10.2337/db11-0550]