• PMID: 19657388
• Gene Name: CBS
• Condition: Unexplained azoospermia, oligozoospermia
• Association: MTHFR, MTRR, CBS
• Mutation: MTHFR (R68Q, A222V and E429A), MTRR; (I22M and S175L), CBS; G307S
• Population size: 366
• Population details: 366 (70 unexplained azoospermia, 182 oligozoospermia, 114 normospermic and fertile men )
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Unexplained azoospermia, oligozoospermia

Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts

Ravel C, Chantot-Bastaraud S, Chalmey C, Barreiro L, Aknin-Seifer I, Pfeffer J, Berthaut I, Mathieu EE, Mandelbaum J, Siffroi JP, McElreavey K, Bashamboo A.

BACKGROUND: The metabolic pathway of folate is thought to influence DNA stability either by inducing single/double stranded breaks or by producing low levels of S-adenosyl-methionine leading to abnormal gene expression and chromosome segregation. Polymorphisms in the genes encoding enzymes in the folate metabolism pathway show distinct geographic and/or ethnic variations and in some cases have been linked to disease. Notably, the gene Methylenetetrahydrofolate reductase (MTHFR) in which the homozygous (TT) state of the polymorphism c.665C>T (p.A222V) is associated with reduced specific activity and increased thermolability of the enzyme causing mild hyperhomocysteinemia. Recently several studies have suggested that men carrying this polymorphism may be at increased risk to develop infertility. METHODOLOGY/PRINCIPAL FINDINGS: We have tested this hypothesis in a case/control study of ethnic French individuals. We examined the incidence of polymorphisms in the genes MTHFR (R68Q, A222V and E429A), Methionine synthase reductase MTRR; (I22M and S175L) and Cystathionine beta-synthase (CBS; G307S). The case population consisted of DNA samples from men with unexplained azoospermia (n = 70) or oligozoospermia (n = 182) and the control population consisted of normospermic and fertile men (n = 114). We found no evidence of an association between the incidence of any of these variants and reduced sperm counts. In addition haplotype analysis did not reveal differences between the case and control populations. CONCLUSIONS/SIGNIFICANCE: We could find no evidence for an association between reduced sperm counts and polymorphisms in enzymes involved in folate metabolism in the French population. FAU - Ravel, Celia AU - Ravel C AD - Human Developmental Genetics, Institut Pasteur, Paris, France. FAU - Chantot-Bastaraud, Sandra AU - Chantot-Bastaraud S FAU - Chalmey, Clementine AU - Chalmey C FAU - Barreiro, Luis AU - Barreiro L FAU - Aknin-Seifer, Isabelle AU - Aknin-Seifer I FAU - Pfeffer, Jerome AU - Pfeffer J FAU - Berthaut, Isabelle AU - Berthaut I FAU - Mathieu, E Emmanuelle AU - Mathieu EE FAU - Mandelbaum, Jacqueline AU - Mandelbaum J FAU - Siffroi, Jean-Pierre AU - Siffroi JP FAU - McElreavey, Ken AU - McElreavey K