The impact of hemochromatosis mutations and transferrin genotype on gonadotropin serum levels in infertile men.
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.


METHODS
Case-control and association study.


METHODS
Clinic of obstetrics and gynecology and university-based research laboratory.


METHODS
127 infertile men (including 97 with idiopathic infertility) and 188 controls of proven fertility.


METHODS
Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP).


METHODS
HFE mutations and transferrin allelic polymorphism, and testosterone, prolactin, and gonadotropin serum levels.


RESULTS
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.


CONCLUSIONS
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.
Buretić-Tomljanović
Alena
A
Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia. alena@medri.hr
Vlastelić
Ivan
I
Radojcić Badovinac
Andelka
A
Starcević-Cizmarević
Nada
N
Nadalin
Sergej
S
Ristić
Smiljana
S
D000328:Adult; D016022:Case-Control Studies; D005640:Follicle Stimulating Hormone / Q000097:blood*; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000097:blood / Q000235:genetics*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D014168:Transferrin / Q000235:genetics*
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone