A large-scale association study to assess the impact of known variants of the human INHA gene on premature ovarian failure.
BACKGROUND
Three variants of the human INHA gene have been reported to be associated with premature ovarian failure (POF) in case-control studies involving a small number of patients and controls. Since inhibin has a fundamental role in the control of ovarian function, it is important to establish the relevance of the reported variants for disease risk.


METHODS
Three independent POF cohorts, recruited in Northern and Central Italy and in Germany consisting of a total of 611 patients and 1084 matched controls, were genotyped for the three variants: -16C > T, -124A > G and 769G > A.


RESULTS
No significant difference was detected between allelic frequencies of the INHA promoter variants between POF patients and controls. The rare allele in the coding variant appeared to be more frequent among the control populations.


CONCLUSIONS
The association between the INHA promoter variants and POF could not be replicated, and our results suggest that this discrepancy is likely to be due to the small sample size of previous studies. The rare allele of the coding variant seems to exert a protective effect against loss of ovarian function, which should be confirmed in additional large and ethnically diverse cohorts.
Corre
Tanguy
T
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 4A2, Via Olgettina 58, 20132 Milano, Italy.
Schuettler
Julia
J
Bione
Silvia
S
Marozzi
Anna
A
Persani
Luca
L
Rossetti
Raffaella
R
Torricelli
Francesca
F
Giotti
Irene
I
Vogt
Peter
P
Toniolo
Daniela
D
D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
C094377:inhibin-alpha subunit; D007265:Inhibins