Association of Klotho Gene Polymorphisms with Type 2 Diabetes Mellitus
KL Gene Polymorphisms and T2DM
DOI:
https://doi.org/10.54393/pjhs.v6i1.2448Keywords:
Diabetes, Genotype, Lipid, Glucose LevelAbstract
Genetic variants in the Klotho gene could influence the way β-cells function and effectively glucose functions, and this might influence the development of Type 2 Diabetes Mellitus. Objectives: To investigate the association between Klotho gene polymorphisms rs677332 and to determine the risk of developing type II diabetes in a case-control study. Methods: This case-control study was conducted from Feb 2024 to July 2024 at the Department of Pathology, Rashid Latif Medical College, Lahore. The total number of participants was n=586, sample n=293 case diabetics and 293 controls. DNA was extracted from blood samples and genotyped using Polymerase Chain Reaction followed by restriction digestion and validated through Sanger sequencing. To evaluate the genetic and clinical data, statistical tests were performed with SPSS version 25.0 and PLINK (v1.07). Logistic regression analysis, adjusted for age, sex, and region, was used to determine associations between Klotho polymorphisms and Type 2 Diabetes Mellitus. Fasting blood glucose levels were used as a reference variable in multiple nominal regression. Results: The SNPs rs677332 polymorphism and type 2 diabetes were significantly correlated, underscoring the importance of age, BMI, and heredity in diabetes risk. Logistic regression confirmed that individuals in the AA genotype were linked to a 73% rise in the likelihood of diabetes (OR=1.73, p=0.004). Conclusions: The rs677332 polymorphism of the Klotho gene may serve as a potential protective factor against Type 2 Diabetes Mellitus. The outcomes report the significance of Klotho gene variants for metabolic health and indicate the possible advantages of genetic screening for early treatment
References
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2020 Aug; 21(17): 6275. doi: 10.3390/Ijms21176275.
Liu Y and Chen M. Emerging Role of Α-Klotho in Energy Metabolism and Cardiometabolic Diseases. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2023 Sep: 102854. doi: 10.1016/J.Dsx.2023.102854. DOI: https://doi.org/10.1016/j.dsx.2023.102854
Navarro-García JA, Salguero-Bodes R, González-Lafuente L, Martín-Nunes L, Rodríguez-Sánchez E, Bada-Bosch T, et al. The Anti-Aging Factor Klotho Protects against Acquired Long QT Syndrome Induced by Uremia and Promoted by Fibroblast Growth Factor 23. BMC Medicine. 2022 Jan; 20(1): 14. doi: 10.1186/s12916-021-02209-9. DOI: https://doi.org/10.1186/s12916-021-02209-9
Jia C, Zhang S, An J, Cheng X, Li P, Zhang X, et al. Genetic Predisposition to Impaired Beta-Cell Function Modifies the Association Between Serum Pyrethroid Levels and the Risk of Type 2 Diabetes: A Gene-Environment Interaction Study. Ecotoxicology And Environmental Safety. 2024 Oct; 284. doi: 10.1016/J.Ecoenv.2024.116948. DOI: https://doi.org/10.1016/j.ecoenv.2024.116948
Jiang S, Young JL, Wang K, Qian Y, Cai L. Diabetic-Induced Alterations in Hepatic Glucose and Lipid Metabolism: The Role of Type 1 and Type 2 Diabetes Mellitus. Molecular Medicine Reports. 2020 Aug; 22(2): 603-611. doi: 10.3892/Mmr.2020.11175. DOI: https://doi.org/10.3892/mmr.2020.11175
Zhao X, An X, Yang C, Sun W, Ji H, Lian F. The Crucial Role and Mechanism of Insulin Resistance in Metabolic Disease. Frontiers in Endocrinology. 2023 Mar; 14: 1149239. doi: 10.3389/fendo.2023.1149239. DOI: https://doi.org/10.3389/fendo.2023.1149239
Ruze R, Liu T, Zou X, Song J, Chen Y, Xu R, et al. Obesity and Type 2 Diabetes Mellitus: Connections in Epidemiology, Pathogenesis, and Treatments. Frontiers in Endocrinology. 2023 Apr; 14(1). doi: 10.3389/fpubh.2022.1047794. DOI: https://doi.org/10.3389/fendo.2023.1161521
Su W, Chen M, Xiao L, Du S, Xue L, Feng R, et al. Association of Metabolic Dysfunction-Associated Fatty Liver Disease, Type 2 Diabetes Mellitus, and Metabolic Goal Achievement with Risk of Chronic Kidney Disease. Frontiers in Public Health. 2022 Nov; 10. doi: 10.3389/fpubh.2022.1047794. DOI: https://doi.org/10.3389/fpubh.2022.1047794
Elfaki I, Mir R, Tayeb F, Alalawy AI, Barnawi J, Dabla PK, et al. Potential Association of The Pathogenic Kruppel-like Factor 14 (KLF14) and Adiponectin (ADIPOQ) SNVs with Susceptibility to T2DM. Endocrine, Metabolic & Immune Disorders-Drug Targets. 2024 Jul; 24(9): 1090-1100. doi: 10.2174/0118715303258744231117064253. DOI: https://doi.org/10.2174/0118715303258744231117064253
Alvarez MF, Fernandez G, Elfrida SS, Gomez ME. Investigation of KLF14 Promoter Methylation in Patients with Type 2 Diabetes. A Preliminary Analysis. Open Access Library Journal. 2024 Oct; 11(10): 1-5. doi: 10.4236/oalib.1111888. DOI: https://doi.org/10.4236/oalib.1111888
Politi C, Roumeliotis S, Tripepi G, Spoto B. Sample Size Calculation in Genetic Association Studies: A Practical Approach. Life. 2023 Jan; 13(1): 235. doi: 10.3390/life13010235. DOI: https://doi.org/10.3390/life13010235
Reed J, Bain S, Kanamarlapudi V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes, Metabolic Syndrome and Obesity. 2021 Aug: 3567-3602. doi: 10.2147/DMSO.S319895. DOI: https://doi.org/10.2147/DMSO.S319895
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of type 2 diabetes mellitus. International journal of molecular sciences. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275. DOI: https://doi.org/10.3390/ijms21176275
Lima JE, Moreira NC, Sakamoto-Hojo ET. Mechanisms Underlying the Pathophysiology of Type 2 Diabetes: From Risk Factors to Oxidative Stress, Metabolic Dysfunction, and Hyperglycemia. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2022 Feb; 874. doi: 10.1016/j.mrgentox.2021.503437. DOI: https://doi.org/10.1016/j.mrgentox.2021.503437
Barbieri M, Prattichizzo F, La Grotta R, Matacchione G, Scisciola L, Fontanella RA, et al. Is It Time to Revise the Fighting Strategy toward Type 2 Diabetes? Sex and Pollution as New Risk Factors. Ageing Research Reviews. 2024 Jul. doi: 10.3389/fcvm.2022.964743. DOI: https://doi.org/10.1016/j.arr.2024.102405
Ortega MA, Fraile-Martínez O, Naya I, García-Honduvilla N, Álvarez-Mon M, Buján J, et al. Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications. Nutrients. 2020 Sep; 12(9): 2749. doi: 10.3390/nu12092749. DOI: https://doi.org/10.3390/nu12092749
Zhang LY, Jin YJ, Jin QS, Lin LY, Zhang DD, Kong LL. Association between Resistin+ 299A/A Genotype and Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus. Gene. 2013 Oct; 529(2): 340-344. doi: 10.1016/j.gene.2013.08.001. DOI: https://doi.org/10.1016/j.gene.2013.08.001
Ayelign B, Negash M, Andualem H, Wondemagegn T, Kassa E, Shibabaw T, et al. Association of IL-10 (− 1082 A/G) and IL-6 (− 174 G/C) Gene Polymorphism with Type 2 Diabetes Mellitus in Ethiopia Population. BMC Endocrine Disorders. 2021 Dec; 21: 1-8. doi: 10.1186/s12902-021-00738-1. DOI: https://doi.org/10.1186/s12902-021-00738-1
Sarray S, Ezzidi I, Moussa S, Abdennebi HB, Mtiraoui N. Association Study between Adiponectin Gene Variants, Serum Levels and The Risk of Type 2 Diabetes in Tunisian Women: Insights from BMI stratification. Cytokine. 2024 Sep; 181. doi: 10.1016/j.cyto.2024.156695. DOI: https://doi.org/10.1016/j.cyto.2024.156695
Mamashli E, Goulding RP, Iranparvar M, Skishahr FS, Siahkouhian M, Ramezanzade R, et al. Association of Adiponectin Gene Single Nucleotide Polymorphisms with Environmental Risk Factors in Type 2 Diabetes Mellitus: An Updated Evidence of Haplotype-Based Analysis Study. Gene. 2025 Jan; 933. doi: 10.1016/j.gene.2024.148816. DOI: https://doi.org/10.1016/j.gene.2024.148816
Cole JB and Florez JC. Genetics of Diabetes Mellitus and Diabetes Complications. Nature reviews nephrology. 2020 Jul; 16(7): 377-390. doi: 10.1038/s41581-020-0278-5. DOI: https://doi.org/10.1038/s41581-020-0278-5
Goodarzi MO and Rotter JI. Genetics Insights in the Relationship between Type 2 Diabetes and Coronary Heart Disease. Circulation Research. 2020; 126(11): 1526-1548. doi: 10.1161/CIRCRESAHA. DOI: https://doi.org/10.1161/CIRCRESAHA.119.316065
Aaldijk AS, Verzijl CR, Jonker JW, Struik D. Biological and Pharmacological Functions of the FGF19-and FGF21-Coreceptor Beta Klotho. Frontiers in Endocrinology. 2023 May; 14. doi: 10.3389/fendo.2023.1150222. DOI: https://doi.org/10.3389/fendo.2023.1150222
Zenoaga-Barbăroșie C, Berca L, Vassu-Dimov T, Toma M, Nica MI, Alexiu-Toma OA, et al. The Predisposition for Type 2 Diabetes Mellitus and Metabolic Syndrome. Balkan Journal of Medical Genetics. 2023 Jul; 26(1): 21-6. doi: 10.2478/bjmg-2023-0003. DOI: https://doi.org/10.2478/bjmg-2023-0003
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