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ORCID ID

Aysegul Bayramoglu : 0000-0001-8567-807X

Gokhan Bayramoglu : 0000-0003-2779-6478

Halil Ibrahım Guler : 0000-0002-7261-6790

Nezaket Coban : 0000-0002-1893-4229

Mustafa Çagatay Korkmaz : 0000-0003-3302-0705

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with a genetic predisposition. Methylenetetrahydrofolatereductase (MTHFR) gene is one of the candidate genes associated with T2DM and diabetic nephropathy (DN). This research was carried out to determine the frequency of the C677T polymorphism (rs1801133) of the MTHFR gene and examine the role of rs1801133 polymorphism in T2DM and DN development.

Methods: DNA was obtained from peripheral blood samples (273 samples) using a DNA isolation kit. MTHFR rs1801133 polymorphism was determined using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and electrophoresis. PCR products were cut by restriction enzyme HiNF I and analyzed by 2% agarose gel electrophoresis. The results were statistically analyzed.

Results: Although MTHFR rs1801133 genotype frequencies showed statistically significant differences between the control and T2DM patient groups (p = 0.001), no statistically significant difference was found between individuals with and without DN.

Conclusions: MTHFR gene rs1801133 polymorphism is related to T2DM but not to DN. CT and TT genotypes can be accepted as genetic markers.

References

  1. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93:137–88.
  2. Ozbayer C, Kurt H, Kebapci MN, Gunes HV, Colak E, Degırmencı I. Effects of genetic variations in the genes encoding NOD1 and NOD2 on T2 diabetes mellitus and insulin resistance. J Clin Pharm Ther. 2017;4:98–102.
  3. Degirmenci I, Ozbayer C, Kebapci MN, Kurt H, Colak E, Gunes HV. Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are efective on MCP1, IL6, IL1β, and TNFα levels in type 2 diabetes and insulin resistance. Inflamm Res. 2019;68:801–14.
  4. Verhulst MJL, Loos BG, Gerdes VEA, Teeuw WJ. Evaluating all potential oral complications of diabetes mellitus. Front Endocrinol (Lausanne). 2019;10:56.
  5. Yin YW, Sun QQ, Zhang BB, Hu AM, Liu HL, Wang Q, et al. Association between the interleukin-6 gene -572 C/G polymorphism and the risk of type 2 diabetes mellitus: A meta-analysis of 11,681 subjects. Ann Hum Genet. 2013;77:106–14.
  6. Poodineh M, Saravani R, Mirhosseini M, Sargazi S. Association of two methylenetetrahydrofolate reductase polymorphisms (rs1801133, rs1801131) with the risk of type 2 diabetes in South-East of Iran. Rep Biochem Mol Biol. 2019;8:178–83.
  7. Zhou TB, Drummen GP, Jiang ZP, Li HY. Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus. Ren Fail. 2015;37:1247–59.
  8. Nunes MKS, Silva AS, Evangelista IWQ, Filho JM, Gomes CNAP, Nascimento RAF, et al. Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators. Diabetol Metab Syndr. 2017;9:84.
  9. Santana Bezerra H, Severo de Assis C, Dos Santos Nunes MK, Wanderley de Queiroga Evangelista I, Modesto Filho J, Alves Pegado Gomes CN, et al. The MTHFR promoter hypermethylation pattern associated with the A1298C polymorphism influences lipid parameters and glycemic control in diabetic patients. Diabetol Metab Syndr. 2019;11:4.
  10. El-Baz R, Settin A, Ismaeel A, Khaleel AA, Abbas T, Tolba W, et al. MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients. J Renin Angiotensin Aldosterone Syst. 2012;13:472–7.
  11. Ma L, Jiang Y, Kong X, Liu Q, Zhao H, Zhao T, et al. Interaction of MTHFR C677T polymorphism with smoking in susceptibility to diabetic nephropathy in Chinese men with type 2 diabetes. J Hum Genet. 2019;64:23–8.
  12. Eroglu Z, Erdogan M, Tetik A, Karadeniz M, Cetinalp S, Kosova B, et al. The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy. Diabetes Metab Res Rev. 2007;23:621–4.
  13. Mao S, Xiang W, Huang S, Zhang A. Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus. Clin Chim Acta. 2014;20:206–10.
  14. Bayramoglu A, Urhan Kucuk M, Guler HI, Abaci O, Kucukkaya Y, Colak E. Is there any genetic predisposition of MMP-9 gene C1562T and MTHFR gene C677T polymorphisms with essential hypertension? Cytotechnology. 2015;67:115–22.
  15. Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: Epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58:1–10.
  16. Chehadeh SWEH, Jelinek HF, Al Mahmeed WA, Tay GK, Odama UO, Elghazaliet GEB, et al. Relationship between MTHFR C677T and A1298C gene polymorphisms and complications of type 2 diabetes mellitus in an Emirati population. Meta Gene. 2016;9:70–5.
  17. Kakavand Hamidi A, Radfar M, Amoli MM. Association between MTHFR variant and diabetic neuropathy. Pharmacol Rep. 2018;70:1–5.
  18. Meng Y, Liu X, Ma K, Zhang L, Lu M, Zhao M, et al. Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility. Mol Genet Genomic Med. 2019;7:e1020.
  19. Rönn T, Ling C. DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes. Epigenomics. 2015;7:451–60.
  20. Gupta A, Sharma S, Lakkakula S, VKS Bhaskar L. Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis. J Renal Inj Prev. 2019;8:175–84.
  21. Ma L, Liu Q, Jiang Y, Zhao H, Zhao T, Cao Y, et al. Genetically elevated circulating homocysteine concentrations increase the risk of diabetic kidney disease in Chinese diabetic patients. J Cell Mol Med. 2019;23:2794–800.
  22. Fekih-Mrissa N, Mrad M, Ibrahim H, Akremi I, Sayeh A, Jaidane A, et al. Methylenetetrahydrofolate Reductase (MTHFR) (C677T and A1298C) Polymorphisms and Vascular Complications in Patients with Type 2 Diabetes. Can J Diabetes. 2017;41:366–71.
  23. Mtiraoui N, Ezzidi I, Chaieb M, Marmouche H, Aouni Z, Chaieb A, et al. MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients. Diabetes Res Clin Pract. 2007;75:99–106.
  24. Rahimi M, Hasanvand A, Rahimi Z, Vaisi-Raygani A, Mozafari H, Rezaei M, et al. Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus. Clin Biochem. 2010;43:1333–9.
  25. Cui WP, Du B, Jia Y, Zhou WH, Liu SM, Cui YC, et al. Is C677T polymorphism in methylenetetrahydrofolate reductase gene a risk factor for diabetic nephropathy or diabetes mellitus in a Chinese population? Arch Med Res. 2012;43:42–50.
  26. Sun J, Xu Y, Zhu Y, Lu H. Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Res Clin Pract. 2004;64:185–90.
  27. Pirozzi FF, Junior EB, Okumura JV, Salvarani M, Bonini-Domingos CR, Ruiz MA. The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients. Arch Endocrinol Metab. 2018;62:21–6.
  28. Yang S, Zhang J, Feng C, Huang G. MTHFR 677T variant contributes to diabetic nephropathy risk in Caucasian individuals with type 2 diabetes: A meta-analysis. Metabolism. 2013;62:586–94.
  29. Chen H, Wei F, Wang L, Wang Z, Meng J, Jia L, et al. MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: A meta-analysis. Int J Clin Exp Med. 2015;8:3662–70.
  30. Ramanathan G, Harichandana B, Kannan S, Elumalai R, Sfd P. Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms. Nephrology (Carlton). 2019;24:155–9.
  31. Xiong X, Lin XK, Xiao X, Qin DP, Zhou DY, Hu JG, et al. Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review. Nephrology (Carlton). 2016;21:5–12.

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