Study On The Susceptible Genes Of Idiopathic Premature Ovarian Failure In Han Chinese Population

Objective: WNT4 gene and FOXL2 gene are critical in female sexual determination and differentiation, also in the development of reproductive organs. The aim of our study was to investigate whether the mutations of WNT4 gene and FOXL2 gene are present in Han Chinese Women with idiopathic premature ovarian failure.Methods: A hundred and forty-five idiopathic POF cases and a family with BPES were recruited and the peripheral blood was collected. Genomic DNA was extracted from peripheral leukocytes with QIAamp DNA Blood Kit. The entire coding region and splice sites were amplified by polymerase chain reaction (PCR) using primers designed by Primer Premier 5.0 software.?All the PCR products were directly sequenced on an ABI 3730XL automated sequencer.Results: Only one novel variation, in WNT4 Exon2 (195C>T), was detected among the women with POF. However, this synonymous variation did not result in a change in amino acid sequence (65Asp>Asp). We also predicted the splicing change of this synonymous mutation using ESE prediction programs. But no change was found between wild type and mutant type. One insertion mutation (1041-1042 insC) in FOXL2 gene, which leaded to elongated protein, was found in the BPES family.Conclusions: This study is the first attempt to investigate the possible role of WNT4 gene in Chinese sporadic cases with POF. It is suggested that WNT4 gene is not a common cause of POF in Han Chinese women. We found an insertion mutation (1041-1042 insC) in FOXL2 gene leaded to elongated protein. Our study has confirmed an association between FOXL2 and POF and expanded the spectrum of mutation of FOXL2 gene in a Chinese population.Objective: BDNF gene and SYCP3 gene are very important in maintaining the follicular development. The aim of our study was to evaluate whether polymorphisms of BDNF gene and SYCP3 gene are associated with idiopathic POF in Han Chinese women.Methods: A hundred and twenty-eight idiopathic POF cases and 200 healthy controls were recruited and the peripheral blood was collected. Genomic DNA was extracted from peripheral leukocytes with QIAamp DNA Blood Kit. Rs925946 and Rs6265 in BDNF were amplified by polymerase chain reaction (PCR) using primers designed by Primer Premier 5.0 software.?All the PCR products were directly sequenced on an ABI 3730XL automated sequencer. Using HapMap Database and Haploview, 6 Tag SNPs were chosen to cover the entire sequence of the gene SYCP3. Matrix-assisted laser desorption/ionization Time-of-flight Mass Spectrometry (MALDI-TOF MS) was used to perform multiple PCR and collect the data. Allele frequencies and genotype distribution were determined by allele-counting method and analyzed.Results: There was no statistically significant difference in the distributions of genotypes and alleles with these polymorphisms of BDNF and SYCP3 in Chinese women with POF comparing with controls. We also did not observe any significant difference in the haplotype analysis based on these polymorphisms.Conclusion: This study is the first attempt to investigate an association of polymorphisms in BDNF gene and SYCP3 gene with the risk of POF in Chinese patients. According to our results, we assume that BDNF gene and SYCP3 gene may not be the possible potential candidate genes causing this rare disease in Han Chinese women.