Volume 11, Issue 1 (4-2013)
IJRM 2013, 11(1): 19-24 |
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Hossein Pashaiefar1 
, Mohammad Hasan Sheikhha * 2, Seyyed Mehdi Kalantar3 , Tahereh Jahaninejad1 , Mohammad Ali Zaimy1 , Nasrin Ghasemi3
, Mohammad Hasan Sheikhha * 2, Seyyed Mehdi Kalantar3 , Tahereh Jahaninejad1 , Mohammad Ali Zaimy1 , Nasrin Ghasemi3
1- Department of Medical Genetics, Medical Faculty, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran , sheikhha@yahoo.com
3- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran , sheikhha@yahoo.com
3- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract: (3138 Views)
Background: Meiotic genes are very important candidates for genes contributing to female and male infertility. Mammalian MutL homologues have dual roles in DNA mismatch repair (MMR) after replication errors and meiotic reciprocal recombination. The MutL homologs, MLH1 and MLH3 , are crucial for meiotic reciprocal recombination and human fertility. In this study the functional polymorphisms of MLH3 C2531T was investigated in Iranian women with unexplained infertility.
Objective: Investigating the association between a common SNP (single nucleotide polymorphism) C2531T in the MLH3 gene and female infertility.
Materials and Methods: In total, 105 women with unexplained infertility as case group and 100 women with at least one child and no history of infertility or abortion as controls were recruited for this association study. The MLH3 C2531T polymorphism was tested by tetra-amplification refractory mutation system-PCR (4P-ARMS-PCR) method.
Results: The MLH3 2531C and T alleles frequencies were 43.33% and 56.67% among infertile patients, and 61.5% and 38.5% among normal controls, respectively. In the patient and control subjects the CC (Pro 844 Pro) genotype frequency of MLH3 C2531T was 4.76% and 25%, the CT (Pro 844 Leu) genotype was 77.15% and 73%, and the TT (Leu 844 Leu) genotype was 19% and 2%, respectively (p=0.0001).
Conclusion: The presence of the polymorphic allele T leads to an increased risk of 2.09 times (OR=2.09, 95% CI=1.38-3.16; p=0.0001) for developing infertility in relation to the control group. Therefore, our data suggest that the MLH3 C2531T polymorphism can be associated with the risk of unexplained infertility in Iranian women.
Objective: Investigating the association between a common SNP (single nucleotide polymorphism) C2531T in the MLH3 gene and female infertility.
Materials and Methods: In total, 105 women with unexplained infertility as case group and 100 women with at least one child and no history of infertility or abortion as controls were recruited for this association study. The MLH3 C2531T polymorphism was tested by tetra-amplification refractory mutation system-PCR (4P-ARMS-PCR) method.
Results: The MLH3 2531C and T alleles frequencies were 43.33% and 56.67% among infertile patients, and 61.5% and 38.5% among normal controls, respectively. In the patient and control subjects the CC (Pro 844 Pro) genotype frequency of MLH3 C2531T was 4.76% and 25%, the CT (Pro 844 Leu) genotype was 77.15% and 73%, and the TT (Leu 844 Leu) genotype was 19% and 2%, respectively (p=0.0001).
Conclusion: The presence of the polymorphic allele T leads to an increased risk of 2.09 times (OR=2.09, 95% CI=1.38-3.16; p=0.0001) for developing infertility in relation to the control group. Therefore, our data suggest that the MLH3 C2531T polymorphism can be associated with the risk of unexplained infertility in Iranian women.
Type of Study: Original Article |
References
1. Randolph JF Jr. Unexplained infertility. Clin Obstet Gynecol 2000; 43: 897-901. [DOI:10.1097/00003081-200012000-00019]
2. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol 2008; 1: 69-76.
3. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med 2008; 14: 1197-1213. [DOI:10.1038/nm.f.1895]
4. Sanderson ML, Hassold TJ, Carrell DT. Proteins involved in meiotic recombination: a role in male infertility? Sys Biol Reprod Med 2008; 54: 57-74.
5. Edelmann W, Cohen PE, Kneitz B, Winand N, Lia M, Heyer J, et al. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet 1999; 21: 123-127. [DOI:10.1038/5075]
6. Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, et al. hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis. Cancer Res 1999: 59: 816-822.
7. Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, Paquis-Flucklinger V. MSH4 acts in conjunction with MLH1 during mammalian meiosis. FASEB J 2000; 14: 1539-1547. [DOI:10.1096/fj.99-0851com]
8. Marcon E, Moens P. MLH1p and MLH3p Localize to Precociously Induced Chiasmata of Okadaic-Acid-Treated Mouse Spermatocytes. Genetics 2003; 165: 2283-2287.
9. Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B. The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination. J Cell Sci 2002; 115: 1611-1622.
10. Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell 1996; 85: 1125-1134. [DOI:10.1016/S0092-8674(00)81312-4]
11. Lipkin SM, Moens PB, Wang V, Lenzi M, Shanmugarajah D, Gilgeous A, et al. Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat Genet 2002; 31: 385-390. [DOI:10.1038/ng931]
12. Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 2001; 29: E88-8.
13. Xu K, Lu T, Zhou H, Bai L, Xiang Y. The role of MSH5 C85T and MLH3C2531T polymorphisms in the risk of male infertility with azoospermia or severe oligozoospermia. Clin Chim Acta 2010; 411: 49-52. [DOI:10.1016/j.cca.2009.09.038]
14. Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT, et al. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet 2000; 24: 27-35. [DOI:10.1038/71643]
15. Taylor NP, Powell MA, Gibb RK, Rader JS, Huettner PC, Thibodeau SN, et al. MLH3 mutation in endometrial cancer. Cancer Res 2006; 66: 7502-7508. [DOI:10.1158/0008-5472.CAN-06-0248]
16. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res 2001; 11: 863-874. [DOI:10.1101/gr.176601]
17. Ferrás C, Zhou XL, Sousa M, Lindblom A, Barros A. DNA mismatch repair gene hMLH3 variants in meiotic arrest. Fertil Steril 2007; 88: 1681-1684. [DOI:10.1016/j.fertnstert.2007.01.063]
18. Kunkel TA, Erie DA. DNA mismatch repair. Annu Rev Biochem 2005; 74: 681-710. [DOI:10.1146/annurev.biochem.74.082803.133243]
19. Iyer RR, Pluciennik A, Burdett V, Modrich PL. DNA mismatch repair: functions and mechanisms. Chem Rev 2006; 106: 302-323. [DOI:10.1021/cr0404794]
20. Jiricny J. The multifacetedmismatch-repair system. Nature RevMol Cell Biol 2006; 7: 335-346. 21. Whitby MC. Making crossovers during meiosis. Biochem Soc Trans 2005; 33: 1451-1455.
21. Whitby MC. Making crossovers during meiosis. Biochem Soc Trans 2005; 33: 1451-1455.
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