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  • Title: Evaluating the role of the FSH receptor gene Thr307-Ala and Asn680-Ser polymorphisms in male infertility and their association with semen quality and reproductive hormones.
    Author: Safarinejad MR, Shafiei N, Safarinejad S.
    Journal: BJU Int; 2011 Jul; 108(2 Pt 2):E117-25. PubMed ID: 21105990.
    Abstract:
    OBJECTIVE: To determine whether Thr(307)-Asn(680) and Ala(307)-Ser(680) polymorphisms of the follicle-stimulating hormone receptor (FSH-R) gene are associated with male infertility, semen quality, and reproductive hormones. PATIENTS AND METHODS: The FSH-R polymorphisms at codons 680 and 307 were analysed by restriction-fragment-length polymorphism (RFLP) in 172 infertile men and in an equal number of age-matched healthy fertile men. Genotyping of the FSH-R gene was performed using the polymerase chain reaction RFLP technique. All of the participants underwent semen analysis, and reproductive hormones were also measured. RESULTS: Allelic frequencies were 29.7% serine (Ser) and 70.3% asparagine (Asn) for fertile men (the control group), and 33.1% Ser and 66.9% Asn for infertile men (P > 0.05). The FSH-R genotype at position 680 was 49.4% (Asn/Asn), 41.9% (Asn/Ser), and 8.7% (Ser/Ser) in the control group and 40.1% (Asn/Asn), 46.5% (Asn/Ser), and 13.4% (Ser/Ser) in infertile men, respectively (P > 0.05, chi-squared test). Allelic frequencies were 33.1% alanine (Ala) and 66.9% threonine (Thr) for the control group, and 37.8% Ala and 62.2% Thr for the infertile men. The frequencies of genotypes at position 307 were 45.5% Thr/Thr, 43% Thr/Ala, and 11.6% Ala/Ala for the control group and 36.1% Thr/Thr, 52.3% Thr/Ala, and 11.6% Ala/Ala for infertile men. No significant association between codon 680 and codon 307 genotypes and infertility was observed (P = 0.076 and P = 0.073, respectively). The odds ratio (OR) values indicated that individuals with the Thr/Thr + Asn/Ser combined genotypes had a > 50% decreased risk for developing infertility (OR = 0.44; 95% confidence interval [CI]: 0.22-0.77; P = 0.006). The patients with heterozygous Thr/Ala + Asn/Ser combined genotype were 2.65 times more susceptible to infertility than the control group (OR = 2.65; 95% CI: 1.74-3.82; P = 0.0053). The FSH-R codon 680 and codon 307 genotypes did not result in different serum FSH levels either in men with normal spermatogenesis (the control group) or in men with oligoasthenoteratozoospermia (infertile men). We did not observe any significant association of FSH-R genotype frequencies with any of the sperm characteristics analysed in either group. CONCLUSIONS: No significant correlation between serum FSH levels and semen characteristics, or fertility status and FSH-R gene polymorphisms was found. The combination of heterozygous Thr/Ala + Asn/Ser genotypes increases the risk for male infertility.
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