Haplotype and mutation analysis of the TGFBR3 gene in Chinese women with idiopathic premature ovarian failure

This study screened the TGFBR3 mutations in Chinese patients with idiopathic premature ovarian failure (POF) to gain a better understanding the genetic aetiology of POF. One hundred twelve Chinese patients with idiopathic POF and 110 women from normal controls were examined. The coding region and respective flanking intronic regions of the TGFBR3 gene were amplified by the PCR, and the DNA fragments were directly sequenced. Twenty-eight sequence variants, including 12 novel variants, were identified. These novel variants included three missense mutations, two synonymous mutations, and seven mutations in the intronic region. Three novel exonic missense variants were p.E458G, p.P824L, and p.I836V. The c.566-216G>A, c.566-71C>T, c.2022T>C, c.2502A>G, and c.2568G>A variants represented significantly different genotype distribution between POF cases and the controls. The binary logistic regression analysis of c.566-216G>A, c.566-71C>T, and c.2502A>G variants were significantly associated with the POF patients and the ATTAG haplotype was most significantly over-represented as compared with controls (P = 0.00121). The ATTGG and GCTGG haplotypes were significantly higher in controls than in patients (P = 0.00113 and 0.00055, respectively). Other less frequent haplotypes, such as GCCGA, was only present in the patients (P = 0.00066). GTTGG was only present in the controls (P = 0.00001). Significant diversity of genotype distribution and haplotype analysis suggested that TGFBR3 mutations may be responsible for the genetic aetiology of idiopathic POF in Chinese patients.