Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism

Abstract

The aim of this study was to investigate the frequency of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in Georgian females with hypothyroidism. Thirty-four patients and 29 healthy individuals were recruited in this study. Polymerase chain reaction-restriction fragment length polymorphism analyses were used for genotyping of MTHFR polymorphisms. The results of this study suggest that the MTHFR C677T variant was significantly associated with hypothyroidism. In addition, in individuals with T allele risk of hypothyroidism significantly increased. Combination of CT/AA genotypes was more prevalent in the hypothyroid patients than in the control group. Thus, C677T polymorphism could be a possible genetic factor contributing to the pathophysiology of hypothyroidism, possibly through hyperhomocysteinemia.

Keywords

hypothyroidism / hyperhomocysteinemia / MTHFR / SNPs / PCR-RFLP

Funding

None.

Conflict of Interest

None declared.

Acknowledgment

We would like to thank all the patients and control subjects who participated in this study.

References

[1] Friso S, Choi SW, Girelli D, et al. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci U S A 2002; 99(08): 5606-5611

[2] Goyette P, Pai A, Milos R, et al. Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 1998; 9(08): 652-656

[3] Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 1994; 7(02): 195-200

[4] Martin YN, Salavaggione OE, Eckloff BW, Wieben ED, Schaid DJ, Weinshilboum RM. Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics. Pharmacogenet Genomics 2006; 16(04): 265-277

[5] Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. N Engl J Med 2003; 349(01): 45-50

[6] Biselli PM, Guerzoni AR, de Godoy MF, et al. Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease. J Thromb Thrombolysis 2010; 29(01): 32-40

[7] Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10(01): 111-113

[8] Ogino S, Wilson RB. Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis. J Hum Genet 2003; 48(01): 1-7

[9] van der Put NM, Gabreëls F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am J Hum Genet 1998; 62(05): 1044-1051

[10] Zhang R, Huo C, Wang X, Dang B, Mu Y, Wang Y. Two common MTHFR gene polymorphisms (C677T and A1298C) and fetal congenital heart disease risk: an updated meta-analysis with trial sequential analysis. Cell Physiol Biochem 2018; 45(06): 2483-2496

[11] Zhou Y, Chen Y, Cao X, et al. Association between plasma homocysteine status and hypothyroidism: a meta-analysis. Int J Clin Exp Med 2014; 7(11): 4544-4553

[12] Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87(02): 489-499

[13] Cantürk Z, Cetinarslan B, Tarkun I, Cantürk NZ, Ozden M, Duman C. Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 2003; 13(10): 971-977

[14] Garber JR, Cobin RH, Gharib H, et al; American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18(06): 988-1028

[15] Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017; 390(10101): 1550-1562

[16] National Center for Disease Control and Public Health. Subclinical iodine-deficiency hypothiroidism and other forms of hypothyroidism; 2018. Available at: Accessed April 15, 2020

[17] Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018; 14(05): 301-316

[18] Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 2004; 24(01): 1-13

[19] Morris MS, Bostom AG, Jacques PF, Selhub J, Rosenberg IH. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis 2001; 155(01): 195-200

[20] Brouns R, Ursem N, Lindemans J, et al. Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. Prenat Diagn 2008; 28(06): 485-493

[21] Kvaratskhelia T, Kvaratskhelia E, Kankava K, Abzianidze E. MTHFR gene C677T polymorphism and levels of DNA methyltransferases in subclinical Hypothyroidism. Georgian Med News 2017; (265): 19-24

[22] Kvaratskhelia T, Kvintradze M, Zarandia M, Kvaratskhelia E, Abzianidze E. Methylation status of the Alu repetitive sequence in subclinical hypothyroidism patients with T677C variant of MTHFR gene. Eur J Hum Genet 2019; 27: 1911

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Global Medical Genetics