International journal of


EISSN: 2313-3724, Print ISSN:2313-626X

Frequency: 12

line decor
line decor

 Volume 6, Issue 6 (June 2019), Pages: 98-102


 Original Research Paper

 Title: Role of C677T polymorphism in the MTHFR gene in Saudi females affected with infertility

 Author(s): Johara Al-Mutawa *


 Department of Obstetrics and Gynecology, College of Medicine, King Khalid University Hospitals, King Saud University, Riyadh, Saudi Arabia

  Full Text - PDF          XML

 * Corresponding Author. 

  Corresponding author's ORCID profile:

 Digital Object Identifier:


The methylenetetrahydrofolate reductase (MTHFR) gene plays a major role in folate metabolism in infertile women. To date, limited studies have implicated the C677T polymorphism in MTHFR with female infertility, which is defined as the failure to accomplish clinical pregnancy with consistent unprotected sexual intercourse for 1 year; this disorder is influenced by various factors, including obesity and it affects in ~15% of couples during the reproductive period. However, limited molecular studies have been conducted pertaining to female infertility. The current study aimed to investigate the correlation between the C677T polymorphism in MTHFR and infertility in a Saudi population. In this study, 300 genomic DNA samples were extracted from 150 infertile and 150 fertile women, and genotyping was performed for the C677T polymorphism in MTHFR by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results revealed that the mutant T allele was significantly associated with infertility (odds ratio [OR] = 1.86; 95% CI = 1.15–2.99; p = 0.009). Additionally, the dominant and recessive modes of inheritance were positively associated with infertility, i.e., TT vs. CT+CC (OR = 2.98; 95% CI = 1.33–6.66; p = 0.005) and TT+CT vs. CC (OR = 1.89; 95% CI = 1.09–3.26; p = 0.02). The current results indicate that the T allele of the C677T polymorphism in MTHFR is a significant risk factor for infertility in women from a Saudi population. 

 © 2019 The Authors. Published by IASE.

 This is an open access article under the CC BY-NC-ND license (

 Keywords: Infertility, Female infertility, Infertile women, Obesity, C677T variant, MTHFR gene

 Article History: Received 13 January 2019, Received in revised form 14 April 2019, Accepted 15 April 2019


No Acknowledgement.

 Compliance with ethical standards

 Conflict of interest:  The authors declare that they have no conflict of interest.


 Al-Mutawa J (2019). Role of C677T polymorphism in the MTHFR gene in Saudi females affected with infertility. International Journal of Advanced and Applied Sciences, 6(6): 98-102

 Permanent Link to this page


 No Figure


 Table 1 Table 2 Table 3 


 References (33) 

  1. Aarabi M, San Gabriel MC, Chan D, Behan NA, Caron M, Pastinen T, and Trasler J (2015). High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Human Molecular Genetics, 24(22): 6301-6313.   [Google Scholar] PMCID: PMC4614702 PMID: 26307085
  2. Al-Mutawa J (2018). Interaction with angiotensin-converting enzyme-encoding gene in female infertility: Insertion and deletion polymorphism studies. Saudi Journal of Biological Sciences, 25(8): 1617-1621.   [Google Scholar] PMCID: PMC6303183 PMID: 30591778
  3. Altmäe S, Stavreus-Evers A, Ruiz JR, Laanpere M, Syvänen T, Yngve A, and Nilsson TK (2010). Variations in folate pathway genes are associated with unexplained female infertility. Fertility and Sterility, 94(1): 130-137.   [Google Scholar]
  4. Artini PG, Uccelli A, Papini F, Simi G, Di Berardino OM, Ruggiero M, and Cela V (2013). Infertility and pregnancy loss in euthyroid women with thyroid autoimmunity. Gynecological Endocrinology, 29(1): 36-41.   [Google Scholar]
  5. Ashraf DM, Ali D, and Azadeh DM (2015). Effect of infertility on sexual function: A cross-sectional study. Journal of Clinical and Diagnostic Research, 9(5): QC01- QC03.   [Google Scholar] PMCID: PMC4484112 PMID: 26155520
  6. Brazdova A, Senechal H, Peltre G, and Poncet P (2016). Immune aspects of female infertility. International Journal of Fertility and Sterility, 10(1): 1-10.   [Google Scholar] PMCID: PMC4845518 PMID: 27123194
  7. Dağ ZÖ and Dilbaz B (2015). Impact of obesity on infertility in women. Journal of the Turkish German Gynecological Association, 16(2): 111-117.   [Google Scholar] PMCID: PMC4456969 PMID: 26097395
  8. Enciso M, Sarasa J, Xanthopoulou L, Bristow S, Bowles M, Fragouli E, and Wells D (2016). Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Human Genetics, 135(5): 555-568.   [Google Scholar]
  9. Eniola OW, Adetola AA, and Abayomi BT (2017). A review of female infertility; Important etiological factors and management. Journal of Microbiology and Biotechnology Research, 2(3): 379-385.   [Google Scholar]
  10. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, and Rozen R (1995). A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nature Genetics, 10(1): 111-113.   [Google Scholar]
  11. Fucharoen S (2007). Genetic polymorphisms and implications for human diseases. Journal of the Medical Association of Thailand, 90(2): 394-398.   [Google Scholar]
  12. Gaskins AJ (2018). Importance of studying infertility from a life course perspective. Fertility and Sterility, 110(4): 628-628.   [Google Scholar]
  13. Gong M, Dong W, He T, Shi Z, Huang G, Ren R, and Yuan R (2015). MTHFR 677C> T polymorphism increases the male infertility risk: A meta-analysis involving 26 studies. PloS One, 10(3): e0121147.   [Google Scholar] PMCID: PMC4368707 PMID: 25793386
  14. Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, and Hotaling J (2017). Female infertility, infertility-associated diagnoses, and comorbidities: A review. Journal of Assisted Reproduction and Genetics, 34(2): 167-177.   [Google Scholar] PMCID: PMC5306404 PMID: 27817040
  15. Khan IA, Shaik NA, Kamineni V, Jahan P, Hasan Q, and Rao P (2015). Evaluation of gestational diabetes mellitus risk in south Indian women based on MTHFR (C677T) and FVL (G1691A) mutations. Frontiers in Pediatrics, 3: 34.   [Google Scholar] PMCID: PMC4419678 PMID: 26000264
  16. Khan IA, Vattam KK, Jahan P, Hasan Q, and Rao P (2016). Importance of glucokinase-258G/A polymorphism in Asian Indians with post-transplant and type 2 diabetes mellitus. Intractable and Rare Diseases Research, 5(1): 25-30.   [Google Scholar] PMCID: PMC4761580 PMID: 26989645
  17. Kim SY, Lim JW, Kim JW, Park SY, and Seo JT (2015). Association between genetic polymorphisms in folate-related enzyme genes and infertile men with non-obstructive azoospermia. Systems Biology in Reproductive Medicine, 61(5): 286-292.   [Google Scholar]
  18. Li SS, Li J, Xiao Z, Ren AG, and Jin L (2014). Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility. Genetics and Molecular Research, 13(3): 6367-6374.   [Google Scholar]
  19. Maddirevula S, Coskun S, Alhassan S, Elnour A, Alsaif HS, Ibrahim N, and Alkuraya FS (2017). Female infertility caused by mutations in the oocyte-specific translational repressor PATL2. The American Journal of Human Genetics, 101(4): 603-608.   [Google Scholar] PMCID: PMC5630161 PMID: 28965844
  20. Masoumi SZ, Parsa P, Darvish N, Mokhtari S, Yavangi M, and Roshanaei G (2015). An epidemiologic survey on the causes of infertility in patients referred to infertility center in Fatemieh Hospital in Hamadan. Iranian Journal of Reproductive Medicine, 13(8): 513-516.   [Google Scholar] PMCID: PMC4637117 PMID: 26568755
  21. Mfady DS, Sadiq MF, Khabour OF, Fararjeh AS, Abu-Awad A, and Khader Y (2014). Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population. Gene, 536(1): 40-44.   [Google Scholar]
  22. Murto T, Kallak TK, Hoas A, Altmäe S, Salumets A, Nilsson TK, and Stavreus‐Evers A (2015). Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to in vitro fertilization pregnancy outcome. Acta Obstetricia et Gynecologica Scandinavica, 94(1): 65-71.   [Google Scholar]
  23. Ni W, Li H, Wu A, Zhang P, Yang H, Yang X, and Jiang L (2015). Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population. Journal of Assisted Reproduction and Genetics, 32(3): 369-374.   [Google Scholar] PMCID: PMC4363235 PMID: 25578539
  24. Nikzad H, Karimian M, Sareban K, Khoshsokhan M, and Colagar AH (2015). MTHFR-Ala222Val and male infertility: A study in Iranian men, an updated meta-analysis and an in silico-analysis. Reproductive Biomedicine Online, 31(5): 668-680.   [Google Scholar]
  25. Qin YT, Zhang Y, Wu F, Su Y, Lu GN, and Wang RS (2014). Association between MTHFR polymorphisms and acute myeloid leukemia risk: A meta-analysis. PloS One, 9(2): e88823.   [Google Scholar] PMCID: PMC3930602 PMID: 24586405
  26. Rafique M and Nuzhat A (2016). Role of obesity in female infertility and assisted reproductive technology (ART) outcomes. Saudi Journal of Obesity, 4(2): 75-79.   [Google Scholar]
  27. Romero-Sánchez C, Gómez-Gutierrez A, Gómez PE, Casas-Gomez MC, and Briceño I (2015). C677t (rs1801133) MTFHR gene polymorphism frequency in a Colombian population. Colombia Médica, 46(2): 75-79.   [Google Scholar]
  28. Settin A, Elshazli R, Salama A, and ElBaz R (2011). Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian women with unexplained recurrent pregnancy loss. Genetic Testing and Molecular Biomarkers, 15(12): 887-892.   [Google Scholar]
  29. Silvestris E, de Pergola G, Rosania R, and Loverro G (2018). Obesity as disruptor of the female fertility. Reproductive Biology and Endocrinology, 16(1): 22-35.   [Google Scholar] PMCID: PMC5845358 PMID: 29523133
  30. Szczepańska M, Mostowska A, Wirstlein P, Lianeri M, Marianowski P, Skrzypczak J, and Jagodziński PP (2011). Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility. European Journal of Obstetrics and Gynecology and Reproductive Biology, 157(1): 67-72.   [Google Scholar]
  31. Thaler CJ, Budiman H, Ruebsamen H, Nagel D, and Lohse P (2006). Effects of the common 677C> T mutation of the 5, 10‐methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle‐stimulating hormone. American Journal of Reproductive Immunology, 55(4): 251-258.   [Google Scholar]
  32. Wang X, Fu J, Li Q, and Zeng D (2016). Geographical and ethnic distributions of the MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in Chinese populations: A meta-analysis. PLoS One, 11(4): e0152414.   [Google Scholar] PMCID: PMC4835080 PMID: 27089387
  33. Zhu X, Liu Z, Zhang M, Gong R, Xu Y, and Wang B (2016). Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: A meta-analysis. Renal Failure, 38(2): 185-193.   [Google Scholar]