International Journal of

ADVANCED AND APPLIED SCIENCES

EISSN: 2313-3724, Print ISSN: 2313-626X

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 Volume 9, Issue 12 (December 2022), Pages: 77-84

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 Original Research Paper

 Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes

 Author(s): Nada Alqadri 1, Nuha A. Abdelmutalab 2, Sitalnesa Abdelhafeez 3, Atyah Y. Alzahrani 4, Omima Gadalla Mohamed 3, Aeshah Hassan 5, Omaima Nasir 1, *

 Affiliation(s):

 1Department of Biology, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
 2Department of Infection Control, King Faisal Medical Complex. P.O. Box 2265, Taif 21944, Saudi Arabia
 3Department of Communicable Diseases Control Directorate, Taif 21944, Saudi Arabia
 4Department of Family Medicine, Directorate, Taif 21944, Saudi Arabia
 5Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

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 * Corresponding Author. 

  Corresponding author's ORCID profile: https://orcid.org/0000-0002-3021-6473

 Digital Object Identifier: 

 https://doi.org/10.21833/ijaas.2022.12.010

 Abstract:

T2DM is a long-term metabolic disorder characterized by either the pancreas' inability to produce enough insulin or the body's inability to properly utilize the insulin it produces. The β-cell function and blood glucose homeostasis are two areas where TCF7L2 (Transcription factor 7 like 2) appears to be a significant candidate gene. KCNQ1 (potassium voltage-gated channel subfamily, member 1 has been discovered as a T2DM susceptibility gene in Asian populations by genome-wide association studies with rs2237892 polymorphism and an increased risk of developing T2DM. The aim of this study was to investigate the association between rs7903146 and rs2237892 SNP studies in T2DM patients. In this study, 60 T2DM cases and 60 controls were selected. Genotyping was performed for rs7903146 and rs2237892 SNPs using specific primers and restriction enzymes, then all PCR products were loaded on an agarose gel stained with ethidium bromide. The current study results confirmed rs7903146 SNP was strongly associated with genotype (OR-4.14; 95%CI:1.07-15.98; p=0.02) and allele frequencies (OR-4.60; 95%CI:1.66-12.70; p=0.001) whereas in rs2237892 SNP was not associated with any of the genotypes (OR-4.29; 95%CI:0.46-39.58; p=0.16; OR-3.21) or allele frequencies (OR-6.26; 95%CI:0.74-52.83; p=0.055). The current study results were found to be associated with global studies carried out in rs7903146 and rs2237892 SNP. The strength of this current study was to involve Saudi nationalities and we have screened rs7903146 and rs2237892 SNPs which plays a major role in T2DM. Involving 60 T2DM cases/60 controls was the major limitation of this study. Missing validation through Sanger sequencing analysis was one of the limitations of this study. In conclusion, the current study results confirmed rs7903146 SNP was strongly associated with T2DM and rs2237892 SNP was not associated with T2DM patients.

 © 2022 The Authors. Published by IASE.

 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

 Keywords: Type 2 diabetes mellitus, Rs7903146, Rs2237892, TCF7L2, KCNQ1

 Article History: Received 12 April 2022, Received in revised form 4 August 2022, Accepted 29 August 2022

 Acknowledgment 

No Acknowledgment.

 Compliance with ethical standards

 IRB details: 

The ethical grant for this study was obtained from Institutional Review Board and a patient-informed consent form was obtained for all subjects who participated in this study. In this study, we have excluded the participants who weren’t signed the consent form. This study was conducted in accordance with the principles outlined in the Helsinki Declaration. This is a case-control study.

 Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

 Citation:

 Alqadri N, Abdelmutalab NA, Abdelhafeez S, Alzahrani AY, Mohamed OG, Hassan A, and Nasir O (2022). Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes. International Journal of Advanced and Applied Sciences, 9(12): 77-84

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 Figures

 Fig. 1 Fig. 2 Fig. 3

 Tables

 Table 1 Table 2 Table 3 Table 4 

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 References (38)

  1. Alharbi KK, Abudawood M, and Khan IA (2021). Amino-acid amendment of arginine-325-tryptophan in rs13266634 genetic polymorphism studies of the SLC30A8 gene with type 2 diabetes-mellitus patients featuring a positive family history in the Saudi population. Journal of King Saud University-Science, 33(1): 101258. https://doi.org/10.1016/j.jksus.2020.101258   [Google Scholar]
  2. Alharbi KK, Alsaikhan AS, Alshammary AF, Al-Hakeem MM, and Khan IA (2022). Screening of mitochondrial mutations in Saudi women diagnosed with gestational diabetes mellitus: A non-replicative case-control study. Saudi Journal of Biological Sciences, 29(1): 360-365. https://doi.org/10.1016/j.sjbs.2021.08.102   [Google Scholar] PMid:35002430 PMCid:PMC8716902
  3. Alharbi KK, Khan IA, and Syed R (2013). Circulating C5L2 gene polymorphism is associated with type 2 diabetes mellitus in Saudi population. Molecular Biology Reports, 40(11): 6323-6327. https://doi.org/10.1007/s11033-013-2745-6   [Google Scholar] PMid:24078164
  4. Alotaibi A, Perry L, Gholizadeh L, and Al-Ganmi A (2017). Incidence and prevalence rates of diabetes mellitus in Saudi Arabia: An overview. Journal of Epidemiology and Global Health, 7(4): 211-218. https://doi.org/10.1016/j.jegh.2017.10.001   [Google Scholar] PMid:29110860 PMCid:PMC7384574
  5. Al-Otaiby M, Althnayan R, Binmethem A, AlEnezy RB, Alhadlg MA, Alaqeel A, and Khan IA (2021). The prevalence of Factor V Leiden (Arg506Gln) mutation in King Khalid University Hospital patients, 2017–2019. Nagoya Journal of Medical Science, 83(3): 407-417. https://doi.org/10.18999/nagjms.83.3.407   [Google Scholar] PMid:34552279 PMCid:PMC8438009
  6. Alqadri N (2022). Independent case-control study in KCNJ11 gene polymorphism with Type 2 diabetes mellitus. Saudi Journal of Biological Sciences, 29(4): 2794-2799. https://doi.org/10.1016/j.sjbs.2022.01.008   [Google Scholar] PMid:35531169 PMCid:PMC9073069
  7. Alshammary AF and Khan IA (2021). Screening of obese offspring of first-cousin consanguineous subjects for the angiotensin-converting enzyme gene with a 287-bp Alu sequence. Journal of Obesity and Metabolic Syndrome, 30(1): 63-71. https://doi.org/10.7570/jomes20086   [Google Scholar] PMid:33653971 PMCid:PMC8017326
  8. Alzaheb RA and Altemani AH (2018). The prevalence and determinants of poor glycemic control among adults with type 2 diabetes mellitus in Saudi Arabia. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 11: 15-21. https://doi.org/10.2147/DMSO.S156214   [Google Scholar] PMid:29430192 PMCid:PMC5797462
  9. Ao D, Wang HJ, Wang LF, Song JY, Yang HX, and Wang Y (2015). The rs2237892 polymorphism in KCNQ1 influences gestational diabetes mellitus and glucose levels: A case-control study and meta-analysis. PLOS ONE, 10(6): e0128901. https://doi.org/10.1371/journal.pone.0128901   [Google Scholar] PMid:26039078 PMCid:PMC4454508
  10. Brown A, McArdle P, Taplin J, Unwin D, Unwin J, Deakin T, and Mellor D (2022). Dietary strategies for remission of type 2 diabetes: A narrative review. Journal of Human Nutrition and Dietetics, 35(1): 165-178. https://doi.org/10.1111/jhn.12938   [Google Scholar] PMid:34323335
  11. Chehadeh SWEH, Jelinek HF, Al Mahmeed WA, Tay GK, Odama UO, Elghazali GE, and Al Safar HS (2016). Relationship between MTHFR C677T and A1298C gene polymorphisms and complications of type 2 diabetes mellitus in an Emirati population. Meta Gene, 9: 70-75. https://doi.org/10.1016/j.mgene.2016.04.002   [Google Scholar] PMid:27222819 PMCid:PMC4856855
  12. Chen Z, Zhang X, Ma G, Qian Q, and Yao Y (2010). Association study of four variants in KCNQ1 with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population. Molecular Biology Reports, 37(1): 207-212. https://doi.org/10.1007/s11033-009-9597-0   [Google Scholar] PMid:19575309
  13. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, and Weiss R (2015). Type 2 diabetes mellitus. Nature Reviews Disease Primers, 1: 15019. https://doi.org/10.1038/nrdp.2015.19   [Google Scholar] PMid:27189025
  14. Ding W, Xu L, Zhang L, Han Z, Jiang Q, Wang Z, and Jin S (2018). Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus. BMC Medical Genetics, 19: 38. https://doi.org/10.1186/s12881-018-0553-5   [Google Scholar] PMid:29514658 PMCid:PMC5842570
  15. Elqadi M, Eweidat K, Abu Sabha M, Yagmour A, Sabarneh A, Nasereddin A, and Ereqat S (2021). Methylenetetrahydrofolate reductase C677T gene polymorphism and the association with dyslipidemia in type 2 diabetic Palestinian patients. Journal of Clinical Laboratory Analysis, 35(10): e23994. https://doi.org/10.1002/jcla.23994   [Google Scholar] PMid:34498771 PMCid:PMC8529134
  16. Erfani T, Sarhangi N, Afshari M, Abbasi D, Meybodi HRA, and Hasanzad M (2020). KCNQ1 common genetic variant and type 2 diabetes mellitus risk. Journal of Diabetes and Metabolic Disorders, 19(1): 47-51. https://doi.org/10.1007/s40200-019-00473-4   [Google Scholar] PMid:32550155 PMCid:PMC7271092
  17. Fareed M, Salam N, Khoja AT, Mahmoud AM, and Ahamed M (2017). Life style related risk factors of type 2 diabetes mellitus and its increased prevalence in Saudi Arabia: A brief review. International Journal of Medical Research and Health Sciences, 6(3): 125-132.   [Google Scholar]
  18. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, and Stefansson K (2006). Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics, 38(3): 320-323. https://doi.org/10.1038/ng1732   [Google Scholar] PMid:16415884
  19. Guewo-Fokeng M, Sobngwi E, Atogho-Tiedeu B, Donfack OS, Noubiap JJN, Ngwa EN, and Mbanya JC (2015). Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon. Journal of Diabetes and Metabolic Disorders, 14: 26. https://doi.org/10.1186/s40200-015-0148-z   [Google Scholar] PMid:25897419 PMCid:PMC4403887
  20. Hussain H, Ramachandran V, Ravi S, Sajan T, Ehambaram K, Gurramkonda VB, and Bhaskar LV (2014). TCF7L2 rs7903146 polymorphism and diabetic nephropathy association is not independent of type 2 diabetes-A study in a south Indian population and meta-analysis. Endokrynologia Polska, 65(4): 298-305. https://doi.org/10.5603/EP.2014.0041   [Google Scholar] PMid:25185853
  21. Jiang G, Luk AO, Tam CH, Ozaki R, Lim CK, Chow EY, and Hong Kong Diabetes Biobank Study Group (2022). Clinical predictors and long-term impact of acute kidney injury on progression of diabetic kidney disease in Chinese patients with type 2 diabetes. Diabetes, 71(3): 520-529. https://doi.org/10.2337/db21-0694   [Google Scholar] PMid:35043149 PMCid:PMC8893937
  22. Jiang HL, Du H, Deng YJ, and Liang X (2021). Effect of KCNQ1 rs2237892 polymorphism on the predisposition to type 2 diabetes mellitus: An updated meta-analysis. Diabetology and Metabolic Syndrome, 13: 75. https://doi.org/10.1186/s13098-021-00683-y   [Google Scholar] PMid:34238370 PMCid:PMC8264960
  23. Khan IA (2021). Do second generation sequencing techniques identify documented genetic markers for neonatal diabetes mellitus? Heliyon, 7(9): e07903. https://doi.org/10.1016/j.heliyon.2021.e07903   [Google Scholar] PMid:34584998 PMCid:PMC8455689
  24. Khan IA, Jahan P, Hasan Q, and Rao P (2019). Genetic confirmation of T2DM meta-analysis variants studied in gestational diabetes mellitus in an Indian population. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 13(1): 688-694. https://doi.org/10.1016/j.dsx.2018.11.035   [Google Scholar] PMid:30641791
  25. Khan IA, Poornima S, Jahan P, Rao P, and Hasan Q (2015a). Type 2 diabetes mellitus and the association of candidate genes in Asian Indian population from Hyderabad, India. Journal of Clinical and Diagnostic Research, 9(11): GC01-GC05. https://doi.org/10.7860/JCDR/2015/14471.6855   [Google Scholar] PMid:26673680 PMCid:PMC4668434
  26. Khan IA, Vattam KK, Jahan P, Mukkavali KK, Hasan Q, and Rao P (2015b). Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and post-transplant diabetes mellitus in the Asian Indian population. Genes and Diseases, 2(3): 276-282. https://doi.org/10.1016/j.gendis.2015.02.009   [Google Scholar] PMid:30258870 PMCid:PMC6150093
  27. Liu XH, Xie CG, An Y, Zhang XX, and Wu WB (2015). Meta-analysis of the association between the rs7903146 polymorphism at the TCF7L2 locus and type 2 diabetes mellitus susceptibility. Genetics and Molecular Research, 14(4): 16856-16862. https://doi.org/10.4238/2015.December.14.12   [Google Scholar] PMid:26681031
  28. Rattanatham R, Settasatian N, Komanasin N, Kukongviriyapan U, Sawanyawisuth K, Intharaphet P, and Settasatian C (2021). Association of combined TCF7L2 and KCNQ1 gene polymorphisms with diabetic micro-and macrovascular complications in type 2 diabetes mellitus. Diabetes and Metabolism Journal, 45(4): 578-593. https://doi.org/10.4093/dmj.2020.0101   [Google Scholar] PMid:33752320 PMCid:PMC8369220
  29. Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, and Bakhtiyari S (2014). Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clinical Laboratory, 60(8): 1269-1276. https://doi.org/10.7754/Clin.Lab.2013.130809   [Google Scholar]
  30. Sun Q, Song K, Shen X, and Cai Y (2012). The association between KCNQ1 gene polymorphism and type 2 diabetes risk: A meta-analysis. PLOS ONE, 7(11): e48578. https://doi.org/10.1371/journal.pone.0048578   [Google Scholar] PMid:23133642 PMCid:PMC3487731
  31. Syamsurizal S, Handayani D, Kadri H, and Badriyya E (2019). Genotyping SNP rs7903146 TCF7L2 gene for detection T2DM in Indonesian Melayu ethnic. In the Journal of Physics: Conference Series, IOP Publishing, Padang, Indonesia, 1317(1): 012090. https://doi.org/10.1088/1742-6596/1317/1/012090   [Google Scholar]
  32. Taheri R, Kazerouni F, Mirfakhraei R, Kalbasi S, Shahrokhi SZ, and Rahimipour A (2022). The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study. Gene, 823: 146382. https://doi.org/10.1016/j.gene.2022.146382   [Google Scholar] PMid:35240257
  33. Turki A, Mtiraoui N, Al-Busaidi AS, Khirallah M, Mahjoub T, and Almawi WY (2012). Lack of association between genetic polymorphisms within KCNQ1 locus and type 2 diabetes in Tunisian Arabs. Diabetes Research and Clinical Practice, 98(3): 452-458. https://doi.org/10.1016/j.diabres.2012.10.006   [Google Scholar] PMid:23107108
  34. Wang T, Maimaitituersun G, Shi H, Chen C, Ma Q, Su Y, and Zhu J (2022a). The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China. Genes and Genomics, 44(4): 499-508. https://doi.org/10.1007/s13258-021-01209-6   [Google Scholar] PMid:35094288 PMCid:PMC8921155
  35. Wang X, Zhang L, Qin L, Wang Y, Chen F, Qu C, and Miao J (2022b). Physicochemical properties of the soluble dietary fiber from laminaria japonica and its role in the regulation of type 2 diabetes mice. Nutrients, 14(2): 329. https://doi.org/10.3390/nu14020329   [Google Scholar] PMid:35057510 PMCid:PMC8779286
  36. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, and Kasuga M (2008). Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nature Genetics, 40(9): 1092-1097. https://doi.org/10.1038/ng.207   [Google Scholar] PMid:18711367
  37. Yu XX, Liao MQ, Zeng YF, Gao XP, Liu YH, Sun W, and Ye YB (2020). Associations of KCNQ1 polymorphisms with the risk of type 2 diabetes mellitus: An updated meta-analysis with trial sequential analysis. Journal of Diabetes Research, 2020: 7145139. https://doi.org/10.1155/2020/7145139   [Google Scholar] PMid:32695830 PMCid:PMC7362295
  38. Zhang W, Wang H, Guan X, Niu Q, and Li W (2015). Variant rs2237892 of KCNQ1 is potentially associated with hypertension and macrovascular complications in type 2 diabetes mellitus in a Chinese Han population. Genomics, Proteomics and Bioinformatics, 13(6): 364-370. https://doi.org/10.1016/j.gpb.2015.05.004   [Google Scholar] PMid:26678516 PMCid:PMC4747647