Association of MTHFR C677T and MTRR A66G Gene Polymorphisms with Iranian Male Infertility and Its Effect on Seminal Folate and Vitamin B12

Document Type : Original Article


1 Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

2 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

3 Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

4 Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran

5 Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran


Background: The relation between key enzymes in regulation of folate metabolism and male infertility is the subject
of numerous studies. We aimed to determine whether 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T
and methionine synthase reductase (MTRR) A66G genotypes are associated with male infertility in Iranian men and
to evaluate its effect on seminal levels of folate and vitamin B12.

Materials and Methods: In this retrospective study, semen and peripheral blood samples were collected from 254
men with oligoasthenoteratozoospermia (OAT) and 77 normozoospermic men who attended Avicenna infertility clinic.
Single nucleotide polymorphism (SNP) analysis was carried out in genomic DNA by polymerase chain reaction
(PCR)-restriction fragment length polymorphism (RFLP) method for MTHFR C677T and MTRR A66G gene polymorphisms.

Results: In MTHFR C677T, our founding showed that T carrier was conversely lower in OAT than normozoospermic men
(χ2-test=7.245, P=0.02) whereas in MTRR A66G, A and G carrier showed no significant difference between the two groups
(χ2-test=1.079, P=0.53). The concentration of seminal folate was not different between normozoospermic (18.83 ± 17.1 ng/
ml) and OAT (16.96 ± 14.2 ng/ml) men (P=0.47). The concentration of vitamin B12 was slightly higher in normozospermic
men (522.6 ± 388.1 pg/ml) compared to OAT men (412.9 ± 303.6 pg/ml, P=0.058).

Conclusion: The MTHFR C677T and MTRR A66G have no effect on the concentrations of seminal folate and vitamin
B12. The present study showed that two SNPs of MTRR A66G and MTHFR C677T cannot be seen as a risk factor for
male factor subfertility.


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