The impact of hemochromatosis mutations and transferrin genotype on gonadotropin serum levels in infertile men
Received 20 September 2007; received in revised form 15 February 2008; accepted 15 February 2008. published online 07 April 2008.
Objective
To address the possibility that HFE mutations and TF gene polymorphism cause dysfunction of spermatogenesis and/or the hypothalamic-pituitary-gonadal axis via contribution to long-term iron overload in the testes and brain.
Design
Case-control and association study.
Setting
Clinic of obstetrics and gynecology and university-based research laboratory.
Patient(s)
127 infertile men (including 97 with idiopathic infertility) and 188 controls of proven fertility.
Intervention(s)
Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP).
Main Outcome Measure(s)
HFE mutations and transferrin allelic polymorphism, and testosterone, prolactin, and gonadotropin serum levels.
Result(s)
The frequencies of the analyzed alleles and genotypes showed no statistically significant difference between infertile men and controls. Sperm count and progressive sperm motility did not correlate with HFE or TF genotype, or their combination. After excluding patients with clinical hypogonadism or varicocele from further analysis, a statistically significant correlation between serum follicle-stimulating hormone and luteinizing hormone levels and the combined HFE H63D/TFC2 genotype was found in 97 men with idiopathic infertility.
Conclusion(s)
The combined HFE H63D/TF-C2 genotype contributed to 4.1% and 10.6% of follicle-stimulating hormone and luteinizing hormone variation, respectively, in infertile men, raising mean hormonal values above the normal physiologic range. Therefore, HFE and TF genes together may influence the hypothalamic-pituitary-gonadal axis, functioning at the pituitary or testes level.
aDepartment of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia
bDepartment of Human Reproduction, Clinic of Obstetrics and Gynaecology, Clinical Medical Centre Rijeka, Rijeka, Croatia
Reprint requests: Alena Buretić-Tomljanović, Ph.D., Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Braće Branchetta 22, 51 000 Rijeka, Croatia (FAX: +385-51-678-896).
A.B-T. has nothing to disclose. I.V. has nothing to disclose. A.R.B. has nothing to disclose. N.S-C. has nothing to disclose. S.N. has nothing to disclose. S.R. has nothing to disclose.
ABSTRACT