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http://dx.doi.org/10.5653/cerm.2018.00423

Investigation of the association of idiopathic male infertility with polymorphisms in the methionine synthase (MTR) gene  

Tanoomand, Asghar (Department of Basic Sciences, Faculty of Medicine, Maragheh University of Medical Sciences)
Hajibemani, Abolfazl (Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz)
Abouhamzeh, Beheshteh (Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences)
Publication Information
Clinical and Experimental Reproductive Medicine / v.46, no.3, 2019 , pp. 107-111 More about this Journal
Abstract
Objective: Spermatogenesis is a complex process that is regulated by a number of genes, some of which are involved in folate-dependent 1-carbon metabolism. Methionine synthase (encoded by MTR) is a key enzyme participating in this pathway. This study aimed to investigate the relationship of the MTR 2756A > G polymorphism with idiopathic male fertility in the Iranian population. Methods: The participants of this study included 100 men with idiopathic infertility and 100 healthy men as the control group. Genotyping of MTR 2756A > G was performed using the polymerase chain reaction and restriction fragment length polymorphism technique. The obtained data were analyzed using SPSS ver. 20.0 with a level of confidence of p< 0.05. Results: The frequencies of the A and G alleles at this locus were 77% and 23% in infertile patients and 84% and 16% in the control group, respectively. The frequencies of the GG, GA, and AA genotypes were 5%, 36%, and 59% in the infertile patients versus 3%, 27%, and 70% in the control group, respectively. No significant difference was observed in any genetic models. Conclusion: In general, the findings of this study suggest that the MTR 2756A > G single-nucleotide polymorphism is not a predisposing factor for idiopathic infertility in men.
Keywords
Idiopathic; Male infertility; MTR; Polymorphism;
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1 Speroff L, Class RH, Kase NG. Clinical gynecologic endocrinology and infertility. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 1999.
2 Ebisch IM, Pierik FH, DE Jong FH, Thomas CM, Steegers-Theunissen RP. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl 2006;29:339-45.   DOI
3 Shefi S, Turek PJ. Definition and current evaluation of subfertile men. Int Braz J Urol 2006;32:385-97.   DOI
4 Lee HC, Jeong YM, Lee SH, Cha KY, Song SH, Kim NK, et al. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Hum Reprod 2006;21:3162-70.   DOI
5 Maclean JA 2nd, Wilkinson MF. Gene regulation in spermatogenesis. Curr Top Dev Biol 2005;71:131-97.   DOI
6 Singh K, Jaiswal D. One-carbon metabolism, spermatogenesis, and male infertility. Reprod Sci 2013;20:622-30.   DOI
7 Crha I, Kralikova M, Melounova J, Ventruba P, Zakova J, Beharka R, et al. Seminal plasma homocysteine, folate and cobalamin in men with obstructive and non-obstructive azoospermia. J Assist Reprod Genet 2010;27:533-8.   DOI
8 Boxmeer JC, Smit M, Weber RF, Lindemans J, Romijn JC, Eijkemans MJ, et al. Seminal plasma cobalamin significantly correlates with sperm concentration in men undergoing IVF or ICSI procedures. J Androl 2007;28:521-7.   DOI
9 Lewis SE, Aitken RJ. DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res 2005;322:33-41.   DOI
10 Weiner AS, Boyarskikh UA, Voronina EN, Tupikin AE, Korolkova OV, Morozov IV, et al. Polymorphisms in folate-metabolizing genes and risk of idiopathic male infertility: a study on a Russian population and a meta-analysis. Fertil Steril 2014;101:87-94.   DOI
11 Nuti F, Krausz C. Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod Biomed Online 2008;16:504-13.   DOI
12 Bentivoglio G, Melica F, Cristoforoni P. Folinic acid in the treatment of human male infertility. Fertil Steril 1993;60:698-701.   DOI
13 Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebocontrolled trial. Fertil Steril 2002;77:491-8.   DOI
14 Hum DW, Bell AW, Rozen R, MacKenzie RE. Primary structure of a human trifunctional enzyme: isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. J Biol Chem 1988;263:15946-50.   DOI
15 Parle-McDermott A, Mills JL, Kirke PN, Cox C, Signore CC, Kirke S, et al. MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae. Am J Med Genet A 2005;132A:365-8.   DOI
16 Direkvand-Moghadam A, Delpisheh A, Khosravi A. Epidemiology of female infertility; a review of literature. Biosci Biotechnol Res Asia 2013;10:559-67.   DOI
17 Kim JH, Jeon YJ, Lee BE, Kang H, Shin JE, Choi DH, et al. Association of methionine synthase and thymidylate synthase genetic polymorphisms with idiopathic recurrent pregnancy loss. Fertil Steril 2013;99:1674-80.   DOI
18 Kurzawski M, Wajda A, Malinowski D, Kazienko A, Kurzawa R, Drozdzik M. Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population. Genet Mol Biol 2015;38:42-7.   DOI
19 Gava MM, Kayaki EA, Bianco B, Teles JS, Christofolini DM, Pompeo AC, et al. Polymorphisms in folate-related enzyme genes in idiopathic infertile Brazilian men. Reprod Sci 2011;18:1267-72.   DOI
20 Carrell DT. Epigenetics of the male gamete. Fertil Steril 2012;97:267-74.   DOI
21 Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med 2001;344:1172-3.   DOI
22 Popp RA, Farcas MF, Trifa AP, Militaru MS, Crisan TO, Pop IV. The methylenetetrahydrofolate dehydrogenase (MTHFD 1) gene G1958A polymorphism and idiopathic male infertility in a Romanian population group. Clujul Med 2012;85:54-8.
23 Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, et al. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril 2003;79 Suppl 3:1597-605.   DOI
24 Khaki AA, Tanoomand A, Hajibemani A, Abouhamzeh B. Detection of polymorphisms in MTHFD1 G1958A and its possible association with idiopathic male infertility. Urol J 2019 Mar 18 [Epub]. http://dx.doi.org/10.22037/uj.v0i0.4647.
25 Balkan M, Atar M, Erdal ME, Rustemoglu A, Yildiz I, Gunesacar R, et al. Possible association of FAS and FASLG polymorphisms with the risk of idiopathic azoospermia in southeast Turkey. Genet Test Mol Biomarkers 2014;18:383-8.   DOI