Clinical and Experimental Reproductive Medicine

  • 제30권4호
  • /
  • Pages.325-331
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  • 2003
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

한국인 남성 불임 환자에서 5,10-Methylenetetrahydrofolate Reductase (MTHFR) 유전자의 1298번의 다형성과의 관련성에 관한 연구

Genetic analysis for Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) A1298C and Infertile Males in Korea

  • 정유미 (차병원 생식의학 및 불임유전체 연구센터) ;
  • 정태규 (차병원 비뇨기과) ;
  • 김현주 (차병원 비뇨기과) ;
  • 이숙환 (차병원 생식의학 및 불임유전체 연구센터) ;
  • 박정훈 (차병원 생식의학 및 불임유전체 연구센터) ;
  • 김남근 (차병원) ;
  • 김세현 (차병원) ;
  • 차광렬 (차병원) ;
  • 이수만 (차병원 생식의학 및 불임유전체 연구센터)
  • Jeong, Yu-Mi (Genome Research Center for Reproductive Medicine and Infertility, CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Chung, Tae-Gue (Department of Urology, CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Kim, Hyun-Joo (Department of Urology, CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Lee, Sook-Hwan (Genome Research Center for Reproductive Medicine and Infertility, CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Park, Jung-Hoon (Genome Research Center for Reproductive Medicine and Infertility, CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Kim, Nam-Keun (CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Kim, Se-Hyun (CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Cha, Kwang-Yul (CHA General Hospital, College of Medicine, Pochon CHA University) ;
  • Lee, Su-Man (Genome Research Center for Reproductive Medicine and Infertility, CHA General Hospital, College of Medicine, Pochon CHA University)
  • 발행 : 2003.12.30
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초록

Objective: To investigate the association of genetic background between MTHFR A1298C genotype and male infertility. Materials and Methods: We compared 377 infertile males with 396 healthy fertile males with one or more offspring. Infertile males were classified into four subtypes (281 azoospermia, 26 oligoasthenoteratozoospermia (OAT), 59 severe OAT and 11 remnants) by World Health Organization (WHO). Pyrosequencing analysis for MTHFR (methylenetetrahydrofolatereductase) A1298C variation was performed on polymerase chain reaction (PCR) product of study group. To validate pyrosequencing data of A1298C variation for randomly selected 50 samples, we compared the pyrosequencing result with the PCR-RFLP (Restriction Fragment Length Polymorphism) result of MTHFR A1298C genotype. Results: We studied MTHFR A1298C variation by pyrosequencing. A1298C variation data (1298 AC; p=0.2166 and 1298 CC; p=0.5056) of MTHFR gene was no significant difference in between fertile and infertile males. Conclusion: The genetic analysis in MTHFR gene didn't appear genetic difference in Korean fertile and infertile males. We require further study for MTHFR gene in infertile males.

키워드

참고문헌

  1. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, et al. Gene structure of human and mouse methyllenetetrahydrofolate reductase (MTHFR). Mamm Genome 1998; 9: 652-6 https://doi.org/10.1007/s003359900838
  2. Fodinger M, Horl WH, Sunder-Plassmann G. Molecular biology of 5,10-methylenetetrahydrofolate re ductase. J Nephrol 2000; 13: 20-33
  3. Chango A, Boisson F, Barbe F, Quilliot D, Droesch S, Pfister M, et al. The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br J Nutr 2000; 83: 593-6 https://doi.org/10.1017/S0007114500000751
  4. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998; 64: 169-72 https://doi.org/10.1006/mgme.1998.2714
  5. Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 1992; 52: 2071s-7s
  6. 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, placebo-controlled trial. Fertil Steril 2002; 77: 491-8 https://doi.org/10.1016/S0015-0282(01)03229-0
  7. Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, et al. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci U S A 1999; 96: 12810-5 https://doi.org/10.1073/pnas.96.22.12810
  8. van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, 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: 1044-51
  9. James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 1999; 70: 495-501
  10. Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med 2001; 344: 1172-3 https://doi.org/10.1056/NEJM200104123441517
  11. Rozen R. Molecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis 1996; 19: 589-94 https://doi.org/10.1007/BF01799831
  12. Starkebaum G, Harlan JM. Endothelial cell injurydue to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77: 1370-6 https://doi.org/10.1172/JCI112442
  13. Loscalzo J. The oxidant stress of hyperhomocyst(e) inemia. J Clin Invest 1996; 98: 5-7 https://doi.org/10.1172/JCI118776
  14. Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W. A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol Hum Reprod 1996; 2: 613-9 https://doi.org/10.1093/molehr/2.8.613
  15. Kruger TF, Menkveld R, Stander FS, Lombard CJ, Van der Merwe JP, van Zyl JA, et al. Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril 1986; 46: 1118-23 https://doi.org/10.1016/S0015-0282(16)49891-2
  16. World Health Organization. WHO laboratory manual for the examination of human semen and semencervical mucus interation. Cambridge: Cambridge University Press; 1993
  17. Simoni M. Molecular diagnosis of Y chromosome microdeletions in Europe: state-of-the-art and quality control. Hum Reprod 2001; 16: 402-9 https://doi.org/10.1093/humrep/16.3.402
  18. Simoni M, Bakker E, Eurlings MC, Matthijs G, Moro E, Muller CR, et al. Laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions. Int J Androl 1999; 22: 292-9 https://doi.org/10.1046/j.1365-2605.1999.00193.x
  19. Ahmadian A, Gharizadeh B, Gustafsson AC, Sterky F, Nyren P, Uhlen M, et al. Single-nucleotide polymorphism analysis by pyrosequencing. Anal Biochem 2000; 280: 103-10 https://doi.org/10.1006/abio.2000.4493
  20. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000; 72: 324-32
  21. Akar N, Akar E, Ozel D, Deda G, Sipahi T. Common mutations at the homocysteine metabolism pathway and pediatric stroke. Thromb Res 2001; 102: 115-20 https://doi.org/10.1016/S0049-3848(01)00226-2