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


RESULTS
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
We could find no evidence for an association between reduced sperm counts and polymorphisms in enzymes involved in folate metabolism in the French population.
Ravel
Celia
C
Human Developmental Genetics, Institut Pasteur, Paris, France.
Chantot-Bastaraud
Sandra
S
Chalmey
Clementine
C
Barreiro
Luis
L
Aknin-Seifer
Isabelle
I
Pfeffer
Jerome
J
Berthaut
Isabelle
I
Mathieu
E Emmanuelle
EE
Mandelbaum
Jacqueline
J
Siffroi
Jean-Pierre
JP
McElreavey
Ken
K
Bashamboo
Anu
A
D001483:Base Sequence; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D017931:DNA Primers; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D013076:Sperm Count
D017931:DNA Primers; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase