A Genetic Association Study of MTHFR C677T Polymorphism with Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.31661/gmj.v8i.1472Keywords:
MTHFR; Metabolic Syndrome; Polymorphism; Variant; Meta-Analysis; Methylenetetrahydrofolate ReductaseAbstract
Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that plays a crucial role as a methyl-group donor in demethylation of homocysteine. The aim of this systematic review and meta-analysis was to study the relationship between MTHFR gene polymorphism and metabolic syndrome (MS). We used search engines and databases such as Science Direct, Google Scholar, Embase, Cochrane Library, and PubMed to identify eligible studies up to 2018. The articles were studied based on keywords including MTHFR, mutation, variant, and polymorphism in combination with MS. Data was analyzed using Comprehensive Meta-Analysis version 2.2.064 software. After extracting the data from seven articles, the total number of subjects was 1280 in the patient group and 1374 in the control group. The odds ratio was estimated to be 1.078 for the allele model of T vs. C (95% confidence interval [CI]: 1.626-0.715), 1.157 for the allele model of CC vs. CT (95% CI: 0.829-1.615), 1.020 for the allele model of CT + TT vs. CC (95% CI: 1.611-0.646) and 0.799 for the allele model of TT vs. CC + CT (95% CI: 1.185-0.539). As well, the results showed no statistically significant correlation between polymorphism genotypes of the MTHFR gene and MS (P<0.05). In general, this study showed that the presence of C677T polymorphism in the MTHFR gene has no effect on the incidence of MS. [GMJ.2019;8:e1472]
References
Maroto-Sánchez B, Lopez-Torres O, Palacios G, González-Gross M. What do we know about homocysteine and exercise? A review from the literature.
Clin Chem Lab Med. 2016;54(10):1561-77.
Frosst P, Blom H, Milos R, Goyette P, Sheppard CA, Matthews R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111-3.
https://doi.org/10.1038/ng0595-111
PMid:7647779
Outinen PA, Patricia C, SARGE KD, MAEDA N, HIRSH J, RIBAU J, et al. Characterization of the stress-inducing effects of homocysteine. Biochem J. 1998;332(1):213-21.
https://doi.org/10.1042/bj3320213
PMid:9576870 PMCid:PMC1219470
van Guldener C, Stehouwer CD, editors. Diabetes mellitus and hyperhomocysteinemia. Seminars in vascular medicine; 2002: Copyright© 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Becker A, Smulders Y, Van Guldener C, Stehouwer C. Epidemiology of homocysteine as a risk factor in diabetes. Metab Syndr Relat Disord. 2003;1(2):105-20.
https://doi.org/10.1089/154041903322294434
PMid:18370632
Li S, Zhu J, Wu L, Peng L, Luo Y, Zhao Y, et al. The association between plasma homocysteine and ambulatory blood pressure variability in patients with untreated hypertension. Clin Chim Acta. 2018;477:32-8.
https://doi.org/10.1016/j.cca.2017.11.042
PMid:29203427
Cai W, Yin L, Yang F, Zhang L, Cheng J. Association between Hcy levels and the CBS844ins68 and MTHFR C677T polymorphisms with essential hypertension. Biomed Rep. 2014;2(6):861-8.
https://doi.org/10.3892/br.2014.357
PMid:25279160 PMCid:PMC4179705
Martos R, Valle M, Morales R, Cañete R, Gavilan MI, Sánchez-Margalet V. Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children. Metabolism. 2006;55(1):72-7.
https://doi.org/10.1016/j.metabol.2005.07.008
PMid:16324922
Lenna S, Han R, Trojanowska M. Endoplasmic reticulum stress and endothelial dysfunction. IUBMB life. 2014;66(8):530-7.
https://doi.org/10.1002/iub.1292
PMid:25130181 PMCid:PMC4181710
Giltay E, Hoogeveen E, Elbers J, Gooren L, Asscheman H, Stehouwer C. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis. 1998;139(1):197-8.
Ghogomu S, Ngolle N, Mouliom R, Asa B. Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon. Genet Mol Res. 2016;15(1):28.
https://doi.org/10.4238/gmr.15017462
PMid:27051013
Zhu B, Wu X, Zhi X, Liu L, Zheng Q, Sun G. Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies. PloS one. 2014;9(7):e102443.
https://doi.org/10.1371/journal.pone.0102443
PMid:25047451 PMCid:PMC4105552
Liew S-C, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10.
https://doi.org/10.1016/j.ejmg.2014.10.004
PMid:25449138
Wu S, Han Y, Hu Q, Zhang X, Cui G, Li Z, et al. Effects of common polymorphisms in the MTHFR and ACE genes on diabetic peripheral neuropathy progression: a meta-analysis. Mol Neurobiol. 2017;54(4):2435-44.
https://doi.org/10.1007/s12035-016-9823-4
PMid:26971290
Russo G, Di Benedetto A, Alessi E, Ientile R, Antico A, Nicocia G, et al. Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes. J Endocrinol Invest. 2006;29(3):201-7.
https://doi.org/10.1007/BF03345540
PMid:16682831
Roffeei SN, Mohamed Z, Reynolds GP, Said MA, Hatim A, Mohamed EHM, et al. Association of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics. Pharmacogenomics. 2014;15(4):477-85.
https://doi.org/10.2217/pgs.13.220
PMid:24624915
Tang R, Liu H, Yuan Y, Xie K, Xu P, Liu X, et al. Genetic factors associated with risk of metabolic syndrome and hepatocellular carcinoma. Oncotarget. 2017;8(21):35403.
https://doi.org/10.18632/oncotarget.15893
PMid:28515345 PMCid:PMC5471064
Chedraui P, Pérez-López F, Escobar G, Espinoza-Caicedo J, Montt-Guevara M, Genazzani A, et al. Polymorphisms of the FTO and MTHFR genes and vascular, inflammatory and metabolic marker levels in postmenopausal women. J Endocrinol Invest. 2016;39(8):885-90.
https://doi.org/10.1007/s40618-016-0443-7
PMid:26902996
Chen A-R, Zhang H-G, Wang Z-P, Fu S-J, Yang P-Q, Ren J-G, et al. C-reactive protein, vitamin B12 and C677T polymorphism of N-5, 10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population. Clin Invest Med. 2010;33(5):290-7.
https://doi.org/10.25011/cim.v33i5.14354
Fakhrzadeh H, Tavakoli J, Amoli M, Mirarefin M, Sharifi F, Ghotbi S, et al. Investigation of the Relation of Methylenetetrahydrofolic Acid MTHFR (C677T) Reduction Gene with Metabolic Syndrome in the Iranian Population: Tehran Homocysteine Study. ijdld. 2009;8(3):289-98.
Kang BS, Ahn DH, Kim NK, Kim JW. Relationship between metabolic syndrome and MTHFR polymorphism in colorectal cancer. J Korean Soc Coloproctol. 2011;27(2):78-82.
https://doi.org/10.3393/jksc.2011.27.2.78
PMid:21602966 PMCid:PMC3092079
Yang B, Fan S, Zhi X, Wang D, Li Y, Wang Y, et al. Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China. Int J Mol Sci. 2014;15(12):21687-702.
https://doi.org/10.3390/ijms151221687
PMid:25429430 PMCid:PMC4284672
Zeman M, Jáachymová M, Jirák R, Vecka M, Tvrzická E, Stankova B, g. Polymorphisms of genes for brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase in depression and metabolic syndrome. Folia Biol. 2010;56(1):19.
Yamada Y, Kato K, Hibino T, Yokoi K, Matsuo H, Segawa T, Watanabe S, Ichihara S, Yoshida H, Satoh K, Nozawa Y. Prediction of genetic risk for metabolic syndrome. Atherosclerosis. 2007 Apr 1;191(2):298-304.
https://doi.org/10.1016/j.atherosclerosis.2006.05.035
PMid:16806226
Ellingrod VL, Miller DD, Taylor SF, Moline J, Holman T, Kerr J. Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C variants. Schizophr Res. 2008;98(1):47-54.
https://doi.org/10.1016/j.schres.2007.09.030
PMid:17976958 PMCid:PMC2271139
Gallou-Kabani C, Junien C. Nutritional epigenomics of metabolic syndrome. Diabetes. 2005;54(7):1899-906.
https://doi.org/10.2337/diabetes.54.7.1899
PMid:15983188
Lu Q, Qiu X, Hu N, Wen H, Su Y, Richardson B. Epigenetics, disease, and therapeutic interventions. Ageing Res Rev. 2006;5(4):449-67.
https://doi.org/10.1016/j.arr.2006.07.001
PMid:16965942
Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004;20(1):63-8.
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