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Methylene Tetrahydrofolate Reductase C677T Gene Polymorphism In Male Infertility

Yıl 2017, , 1 - 4, 01.01.2017
https://doi.org/10.5455/umj.20170402052343

Öz

Background: Methylenetetrahydrofolate reductase is an important enzyme which plays a major role in folate metabolism and DNA methylation. The objective of this study was to analyze the MTHFR C677T polymorphism in infertile men. Study Design: Blood samples were collected from 58 infertile men and 55 control subjects were taken which are fertile. C677T mutation analysis was done by Polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP Method. Results: The present study reveals that 23 Homozygous CC, 28 heterozygous CT, 7 TT were found in infertile men, whereas in control, the allele variations were 38 Homozygous CC, 17 heterozygous CT, but no Homozygous TT was found. Conclusion: As a result, Genotypes and allele frequencies found in infertile patients and controls but mutant allele was found only in infertile men. Homozygous TT was observed only in azoospermia infertile men whereas heterozygous CT was found in both oligozoospermia and azoospermia subjects. The study has to be extended with a large number of samples.

Kaynakça

  • 1. Ravel C, Chantot-Bastaraud S, Chalmey C, Barreiro L, Aknin-Seifer I, et al. Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts. Plos One 4: e6540.
  • 2. A ZC, Yang Y, Zhang SZ, Li N, Zhang W. Single nucleotide polymorphism 677C.T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia. Asian J Androl 9: 57–62. 3.
  • 3. Lee HC, Jeong YM, Lee SH, Cha KY, Song SH, et al. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Hum Reprod 21: 3162–3170.
  • 4. Dhillon VS, Shahid M, Husain SA. Associations of MTHFR DNMT3b 4977bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in non-obstructive Infertility in Indian men. Mol Hum Reprod 13: 213–222. 5.
  • 5. Chen Z, Karaplis AC, Ackerman SL, Pogribny IP, Melnyk S, et al. Mice deficient in methylenetethrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 10: 433–443.
  • 6. Minocherhomji S, Madon PF, Parikh FR. Epigenetic regulatory mechanisms associated with infertility. Obstet Gynecol Int pii. 198709 p.
  • 7. Khazamipour N, Noruzinia M, Fatehmanesh P, Keyhanee M, Pujol P. MTHFR promoter hypermethylation in testicular biopsies of patients with nonobstructive azoospermia: the role of epigenetics in male infertility. Hum Reprod 24: 2361–2364.
  • 8. Singh K, Singh SK, Raman R. MTHFR A1298C polymorphism and idiopathic male infertility. J Postgrad Med 56: 267–269.
  • 9. Rai V, Yadav U, Kumar P. Prevalence of methylenetetrahydrofolate reductase C677T polymorphism in eastern Uttar Pradesh. Indian J Hum Genet 2012;18:43-6.
  • 10.Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between Genetic Polymorphisms of Methylenetetrahydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility. Reprod Sci 18: 304–315.
  • 11.Bezold G, Lange M, Peter RU. Homozygous methylenetetra hydrofolate reductase 677C.T mutation and male infertility. N Engl J Med 344: 1172–1173.
  • 12.Singh K, Singh SK, Sah R, Singh I, Raman R. Mutation 677C.T in the methylenetetrahydrofolate reductase gene is associated with male infertility in Indian population. Int J Androl 28: 115–119.
  • 13.Park JH, Lee HC, Jeong YM, Chung TG, Kim HJ, et al. MTHFR 677C.T polymorphism associates with unexplained infertile male factors. J Assist Reprod Genet 22: 361–368.
  • 14.Stuppia L, Gatta V, Scarciolla O, Colosimo A, Guanciali-Franchi P, et al. The methylenetethrahydrofolate reductase (MTHFR) 677C.T polymorphism and male infertility in Italy. J Endocrinol Invest 26: 620–622.
  • 15.Ebisch IMW, van Heerde WL, Thomas CM, van der Put N, Wong WY, et al. 677C.T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration. Fertil Steril 80: 1190–1194.
  • 16.Paracchini V, Garte S, Taioli E. MTHFR 677C.T polymorphism, GSTM1 deletion and male infertility: a possible suggestion of a gene/gene interaction? Biomarkers 11: 53–60.
  • 17.Tetik A, Aliyeva U, Cetintas VB, Semerci B, Topcuoglu N, et al. Influence of methylenetetrahydrofolate reductase (MTHFR) 677C.T and 1298 A.C gene polymorphisms on male infertility in turkish infertile men with azoospermia and oligozoospermia. Eur Urol Suppl 7: 92.
  • 18.Gava MM, de Oliveira Chagas E, Bianco B, Christofolini DM, Pompeo AC, et al. Methylenetetrahydrofolate Reductase Polymorphisms Are Related to Male Infertility in Brazilian Men. Genet Test Mol Biomarkers 15: 153–157.
  • 19.Montjean D, Benkhalifa M, Dessolle L, Cohen-Bacrie P, Belloc S, et al. Polymorphisms in MTHFR and MTRR genes associated with blood plasma homocysteine concentration and sperm counts. Fertil Steril 95: 635–640.
  • 20. Lee S, Jeong YM, Lee SK, Cha KY, Chung TG, et al. The 677 C.T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene associates with unexplained male infertility with severe OAT. Fertil Steril 80: 229.
  • 21.Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, et al. Mortality risk in men is associated with a common mutation in the methylenetetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet 7: 197–204.
  • 22. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: 111–113.
  • 23.Van der Put NM, Gabree¨ls F, Stevens EM, Smeitink JA, Trijbels FJ, et al. A second common mutation in the methylenetetrahydro folate reductase gene: An additional risk factor for Neural-Tube Defects. Am J Hum Genet 62: 1044–1051.
  • 24.Gupta N, Gupta S, Dama M, David A, Khanna G, et al. Strong Association of 677 C.T Substitution in the MTHFR Gene with Male Infertility - A Study on an Indian Population and a Meta-Analysis. PLoS ONE 6(7): e22277. doi:10.1371/journal.pone.0022277
  • 25.Raman R, Narayan G. 5-Aza deoxyCytidine-induced inhibition of differentiation of spermatogonia into spermatocytes in the mouse. Mol Reprod Dev 42: 284–290.
  • 26.Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, et al. CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl 23: 815–818
  • 27.Gupta N, Sarkar S, David A, Gangwar PK, Gupta R, et al. Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk. PLoS ONE 8(7): e69180. doi:10.1371/journal.pone. 0069180.
  • 28. Frosst P, Blom HJ, Milos R, Goyette P, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylene tetrahydrofolate reductase. Nat. Genet. 10: 111-113.
  • 29.Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility S.-S. Li1, J. Li1, Z. Xiao2, A.-G. Ren3.
  • 30.Zhu X, Liu Z, Zhang M, Gong R, Xu Y, Wang B. Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis. Ren Fail. 2016 Mar;38(2):185-93.
  • 31.Mancheng Gong, Wenjing Dong, Tingyu He, Zhirong Shi, Guiying Huang,Rui Ren, Sichong Huang, Shaopeng Qiu and Runqiang Yuan MTHFR 677C>T Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies. PLoS One. 2015; 10(3): e0121147.
  • 32.Han-Chul Lee, Yu-Mi Jeong, Sook Hwan Lee, Kwang Yul Cha, Seung-Hun Song,Nam Keun Kim, Kyo Won Lee and Suman Lee. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Hum. Reprod. 21 (12):3162-3170.
Yıl 2017, , 1 - 4, 01.01.2017
https://doi.org/10.5455/umj.20170402052343

Öz

Kaynakça

  • 1. Ravel C, Chantot-Bastaraud S, Chalmey C, Barreiro L, Aknin-Seifer I, et al. Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts. Plos One 4: e6540.
  • 2. A ZC, Yang Y, Zhang SZ, Li N, Zhang W. Single nucleotide polymorphism 677C.T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia. Asian J Androl 9: 57–62. 3.
  • 3. Lee HC, Jeong YM, Lee SH, Cha KY, Song SH, et al. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Hum Reprod 21: 3162–3170.
  • 4. Dhillon VS, Shahid M, Husain SA. Associations of MTHFR DNMT3b 4977bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in non-obstructive Infertility in Indian men. Mol Hum Reprod 13: 213–222. 5.
  • 5. Chen Z, Karaplis AC, Ackerman SL, Pogribny IP, Melnyk S, et al. Mice deficient in methylenetethrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 10: 433–443.
  • 6. Minocherhomji S, Madon PF, Parikh FR. Epigenetic regulatory mechanisms associated with infertility. Obstet Gynecol Int pii. 198709 p.
  • 7. Khazamipour N, Noruzinia M, Fatehmanesh P, Keyhanee M, Pujol P. MTHFR promoter hypermethylation in testicular biopsies of patients with nonobstructive azoospermia: the role of epigenetics in male infertility. Hum Reprod 24: 2361–2364.
  • 8. Singh K, Singh SK, Raman R. MTHFR A1298C polymorphism and idiopathic male infertility. J Postgrad Med 56: 267–269.
  • 9. Rai V, Yadav U, Kumar P. Prevalence of methylenetetrahydrofolate reductase C677T polymorphism in eastern Uttar Pradesh. Indian J Hum Genet 2012;18:43-6.
  • 10.Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between Genetic Polymorphisms of Methylenetetrahydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility. Reprod Sci 18: 304–315.
  • 11.Bezold G, Lange M, Peter RU. Homozygous methylenetetra hydrofolate reductase 677C.T mutation and male infertility. N Engl J Med 344: 1172–1173.
  • 12.Singh K, Singh SK, Sah R, Singh I, Raman R. Mutation 677C.T in the methylenetetrahydrofolate reductase gene is associated with male infertility in Indian population. Int J Androl 28: 115–119.
  • 13.Park JH, Lee HC, Jeong YM, Chung TG, Kim HJ, et al. MTHFR 677C.T polymorphism associates with unexplained infertile male factors. J Assist Reprod Genet 22: 361–368.
  • 14.Stuppia L, Gatta V, Scarciolla O, Colosimo A, Guanciali-Franchi P, et al. The methylenetethrahydrofolate reductase (MTHFR) 677C.T polymorphism and male infertility in Italy. J Endocrinol Invest 26: 620–622.
  • 15.Ebisch IMW, van Heerde WL, Thomas CM, van der Put N, Wong WY, et al. 677C.T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration. Fertil Steril 80: 1190–1194.
  • 16.Paracchini V, Garte S, Taioli E. MTHFR 677C.T polymorphism, GSTM1 deletion and male infertility: a possible suggestion of a gene/gene interaction? Biomarkers 11: 53–60.
  • 17.Tetik A, Aliyeva U, Cetintas VB, Semerci B, Topcuoglu N, et al. Influence of methylenetetrahydrofolate reductase (MTHFR) 677C.T and 1298 A.C gene polymorphisms on male infertility in turkish infertile men with azoospermia and oligozoospermia. Eur Urol Suppl 7: 92.
  • 18.Gava MM, de Oliveira Chagas E, Bianco B, Christofolini DM, Pompeo AC, et al. Methylenetetrahydrofolate Reductase Polymorphisms Are Related to Male Infertility in Brazilian Men. Genet Test Mol Biomarkers 15: 153–157.
  • 19.Montjean D, Benkhalifa M, Dessolle L, Cohen-Bacrie P, Belloc S, et al. Polymorphisms in MTHFR and MTRR genes associated with blood plasma homocysteine concentration and sperm counts. Fertil Steril 95: 635–640.
  • 20. Lee S, Jeong YM, Lee SK, Cha KY, Chung TG, et al. The 677 C.T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene associates with unexplained male infertility with severe OAT. Fertil Steril 80: 229.
  • 21.Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, et al. Mortality risk in men is associated with a common mutation in the methylenetetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet 7: 197–204.
  • 22. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: 111–113.
  • 23.Van der Put NM, Gabree¨ls F, Stevens EM, Smeitink JA, Trijbels FJ, et al. A second common mutation in the methylenetetrahydro folate reductase gene: An additional risk factor for Neural-Tube Defects. Am J Hum Genet 62: 1044–1051.
  • 24.Gupta N, Gupta S, Dama M, David A, Khanna G, et al. Strong Association of 677 C.T Substitution in the MTHFR Gene with Male Infertility - A Study on an Indian Population and a Meta-Analysis. PLoS ONE 6(7): e22277. doi:10.1371/journal.pone.0022277
  • 25.Raman R, Narayan G. 5-Aza deoxyCytidine-induced inhibition of differentiation of spermatogonia into spermatocytes in the mouse. Mol Reprod Dev 42: 284–290.
  • 26.Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, et al. CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl 23: 815–818
  • 27.Gupta N, Sarkar S, David A, Gangwar PK, Gupta R, et al. Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk. PLoS ONE 8(7): e69180. doi:10.1371/journal.pone. 0069180.
  • 28. Frosst P, Blom HJ, Milos R, Goyette P, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylene tetrahydrofolate reductase. Nat. Genet. 10: 111-113.
  • 29.Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility S.-S. Li1, J. Li1, Z. Xiao2, A.-G. Ren3.
  • 30.Zhu X, Liu Z, Zhang M, Gong R, Xu Y, Wang B. Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis. Ren Fail. 2016 Mar;38(2):185-93.
  • 31.Mancheng Gong, Wenjing Dong, Tingyu He, Zhirong Shi, Guiying Huang,Rui Ren, Sichong Huang, Shaopeng Qiu and Runqiang Yuan MTHFR 677C>T Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies. PLoS One. 2015; 10(3): e0121147.
  • 32.Han-Chul Lee, Yu-Mi Jeong, Sook Hwan Lee, Kwang Yul Cha, Seung-Hun Song,Nam Keun Kim, Kyo Won Lee and Suman Lee. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Hum. Reprod. 21 (12):3162-3170.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Research Article
Yazarlar

Papitha P Anand Bu kişi benim

Vijaya Anand Arumugam Bu kişi benim

Chandra R Samuel Bu kişi benim

Yayımlanma Tarihi 1 Ocak 2017
Yayımlandığı Sayı Yıl 2017

Kaynak Göster

Vancouver Anand PP, Arumugam VA, Samuel CR. Methylene Tetrahydrofolate Reductase C677T Gene Polymorphism In Male Infertility. ULUTAS MED J. 2017;3(1):1-4.