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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Multilocus analyses of estrogen-related genes reveal involvement of the ESR1 gene in male infertility and the polygenic nature of the pathology.

OBJECTIVE: To examine whether polymorphisms within the ESR1, FSHR, ESR2, CYP19A1, and NRIP1 genes are susceptibility factors for human male idiopathic infertility and to test the joint effects of these genes on male reproductive function. DESIGN: Genetic association study of male infertility with polymorphisms, using both single-gene and multilocus approaches. SETTING: Private and public fertility units and a private center for biomedical research. PATIENT(S): One hundred four Spanish men with azoospermia or severe oligozoospermia and 95 unselected race-matched healthy controls from the same geographic region. INTERVENTION(S): Peripheral blood extraction, DNA purification, and ESR1 g.938T>C, FSHR Ser680Asn, ESR2 *39A>G, CYP19A1 *19C>T, and NRIP1 Gly75Gly polymorphism analyses. MAIN OUTCOME MEASURE(S): Single-gene statistical analyses and multilocus statistical analyses with Sumstat, Permutation and Model-free analysis, and Estimating Haplotypes software. RESULT(S): We observed an excess of homozygous infertile men for the ESR1 g.938T>C marker. Multilocus analyses detected genetic interaction between the five candidate gene markers that are influential over male infertility. In addition, we detected a five-loci protector genetic pattern with a frequency of 9.4% in controls but absent in infertile men. CONCLUSION(S): Our results support a relevant role for the estrogenic pathway, notably the ESR1 gene, in human male reproductive function and advocate a complex trait model for male infertility.[1]

References

  1. Multilocus analyses of estrogen-related genes reveal involvement of the ESR1 gene in male infertility and the polygenic nature of the pathology. Galan, J.J., Buch, B., Cruz, N., Segura, A., Moron, F.J., Bassas, L., Martinez-Pineiro, L., Real, L.M., Ruiz, A. Fertil. Steril. (2005) [Pubmed]
 
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