Folate and vitamin B12 in idiopathic male infertility

• Published in: Asian journal of andrology Vol. 13; no. 6; pp. 856 - 861
• Main Authors: Murphy, Laurel E, Mills, James L, Molloy, Anne M, Qian, Cong, Carter, Tonia C, Strevens, Helena, Wide-Swensson, Dag, Giwercman, Aleksander, Levine, Richard J
• Format: Journal Article
• Language: English
• Published: China Medknow Publications & Media Pvt. Ltd 01.11.2011; Nature Publishing Group
• Subjects: Adult; Case-Control Studies; Folic Acid - blood; Homocysteine - blood; Humans; Infertility, Male - blood; logistic回归; Male; Middle Aged; Original; Sweden; Vitamin B 12 - blood; 代谢产物; 同型半胱氨酸; 四氢叶酸; 男性不育症; 磷脂酰乙醇胺; 精液质量; 维生素B12; Sweden
• ISSN: 1008-682X; 1745-7262; 1745-7262
• DOI: 10.1038/aja.2011.96

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B12 （B12） and total homocysteine （tHcy）-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmo and Lund, Sweden. Serum folate, red cell folate （RCF）, serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/ homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase （PEMT） M 175V and TCblR rs173665 polymorphisms were significantly associated with infertility （P=0.01 and P=0.009, respectively）, but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men （12.89 vs. 14.73 nmoll^- 1 P=0.02）, but there were no significant differences in RCF, B 12 or tHcy. Folate, B 12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMTand TCbIR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility.