Objective: To assess the influence of length of the alanine tract of forkhead box E1 (FOXE1) gene on genetic susceptibility to idiopathic premature ovarian failure (POF).
Methods: Totally 110 patients with idiopathic POF were recruited between February 2009 and December 2012 at the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University. Controls (n = 110) were individuals with normal menstrual cycles, normal FSH concentrations. The polyalanine tract and flanking sequence of FOXE1 were screened using the multiplex ligation-dependent probe amplification (MLPA) technique and direct sequence technique.
Results: The most frequent of FOXE1 polyalanine stretch length was 14 residues in both groups. The length of FOXE1 polyalanine reported in this study varied from 12 to 16 alanines, and three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. The most common genotypes were 14/14 homozygote, occurring with the frequency of 81.8% (90/110) in the POF group, while 96.4% (106/110) in control subjects, respectively. The incidence of 14/14 genotypes of FOXE1-polyalanine was significantly lower in patients with POF (χ² = 119.730, P = 0.001) in comparison to the controls. There were significantly higher frequencies of the 16/16 genotypes in cases with POF [10.0% (11/110) versus 0; χ² = 3.403, P = 0.001], as compared with the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group than the controls [84.5% (186/220) versus 98.2% (216/220); χ² = 25.923, P = 0.001]. The FOXE1 16 alanine allele was significantly more common in the POF patient group than the controls [12.7% (28/220) versus 1.8% (4/220); χ² = 19.412, P = 0.001].
Conclusions: The polymorphism of the polyalanine tract of FOXE1 gene have a certain relevance for the genetic aetiology of idiopathic POF.