Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population: MTHFD, DHFR and male infertility

被引：0

作者：

Nour El Houda Bousnane ^{[1
]}

Abed Alkarem Abu Alhaija ^{[2
]}

Housna Labed ^{[3
]}

Anissa Fizazi ^{[2
]}

Chahinez Amira Dahmani ^{[4
]}

May Fouad Sadiq ^{[1
]}

机构：

[1] Department of Biology, Faculty of Natural and Life Sciences, University of Oran, 1 Ahmed Ben Bella, Oran

[2] Laboratory of Acquired and Constitutional Genetic Diseases, Faculty of Medicine, University of Batna 2, Batna

[3] Division of Oral Bioscience, Dublin Dental University Hospital, and University of Dublin, Trinity College Dublin, Dublin

[4] Department of Ecology and Environment, Faculty of Natural and Life Sciences, University of Batna 2, Batna

[5] Biology of Development and Differentiation Laboratory, Department of Biology, Faculty of Natural and Life Sciences, University of Oran 1, Oran

[6] Department of Biology, Faculty of Natural and Life Sciences, University Of Mostaganem, Mostaganem

[7] Department of Biological Sciences, Faculty of Sciences, Yarmouk University, Irbid

来源：

Middle East Fertility Society Journal | / 30卷 / 1期

关键词：

DHFR-19bp; Folate metabolism; Male infertility; MTHFD1C401T; MTHFD1G1958A; Semen criteria;

D O I：

10.1186/s43043-025-00223-y

中图分类号：

学科分类号：

摘要：

Background: Methylenetetrahydrofolate dehydrogenase (MTHFD1) and Dihydrofolate reductase (DHFR) are pivotal enzymes in the folate metabolic pathway, playing essential roles in DNA synthesis, repair, and methylation processes critical for spermatogenesis. Numerous studies have implicated genetic variations in their encoding genes in the susceptibility to diverse diseases, including reproductive disorders. Objective: The aim of our study is to investigate the potential association between MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp polymorphisms, sperm parameters, and the risk of idiopathic male infertility. Methods: We conducted a case–control study involving 104 infertile men and 104 controls. Genomic DNA was extracted from blood samples using a commercially kit, and molecular analyses were carried out through direct PCR and PCR–RFLP. Results: Statistical analysis showed significant associations of MTHFD1G1958A and MTHFD1T401C mutant genotypes with male infertility (P < 0.05). The MTHFD1958AA polymorphism was linked to reduced sperm mobility, vitality, and normal morphology (P = 0.001, P = 0.048, P ≤ 0.0001, respectively). MTHFD1T401C was significantly associated with vital sperm (P = 0.009). No significant association was found for the DHFR-19bp polymorphism. Conclusion: This study suggests that MTHFD1G1958A and MTHFD1T401C polymorphisms may contribute to unexplained male infertility, with the MTHFD1 1958GA linked to defects sperm parameters. © The Author(s) 2025.

引用

共 53 条

[1]

Lee H.C., Jeong Y.M., Lee S.H., Cha K.Y., Song S., Kim N.M., Lee K.W., Lee S., Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility, Hum Reprod, 21, pp. 3162-3170, (2006)

[2]

Karimian M., Parvaresh L., Behjati M., Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives, Expert Rev Mol Diagn, 21, 11, pp. 1191-1210, (2021)

[3]

Kurzawski M., Wajda A., Malinowski D., Kazienko A., Kurzawa R., Drozdzik M., Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population, Genet Mol Biol, 38, 1, pp. 42-47, (2015)

[4]

Levine A.J., Lee W., Figueiredo J.C., Conti D.V., Vanderburg D.J., Davis B.D., Edlund C.K., Henning S.M., Heber D., Stern M.C., Haile R.W., Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study, Cancer Causes Control, 22, 4, pp. 541-552, (2011)

[5]

Aleksandra M., Adam P., Tytus M., Nicholas B., Sandrine T., Hippocampal neurogenesis in Alzheimer's disease: Is there a role for dietary modulation?, J Alzheimers Dis, 38, pp. 11-38, (2014)

[6]

Song J., Medline A., Mason J.B., Gallinger S., Kim Y.I., Effects of dietary folate on intestinal tumorigenesis in the Apc(Min) mouse, Cancer Res, 60, 19, pp. 5434-5440, (2000)

[7]

Stanger O., Fowler B., Pietrzik K., Huemer M., Haschke-Becher E., Semmler A., Lorenzl S., Linnebank M., Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations, Expert Rev Neurother, 9, 9, pp. 1393-1412, (2009)

[8]

Liu K., Zhao R., Shen M., Ye J., Li X., Huang Y., Wang Z., Li J., Role of genetic mutations in folate-related enzyme genes on male infertility, Sci Rep, 5, (2015)

[9]

Bhaskar L.V., Murthy J., Venkatesh B.G., Polymorphisms in genes involved in folate metabolism and orofacial clefts, Arch Oral Biol, 56, pp. 723-737, (2011)

[10]

Cabo R., Hernes S., Slettan A., Haugen M., Ye S., Blomhoff R., Mansoor M.A., Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: A randomized, double-blind, crossover study, Genes Nutr, 10, (2015)

← 1 2 3 4 5 6 →