BAX pro-apoptotic gene alterations in repeated pregnancy loss

INTRODUCTION: Recurrent pregnancy loss (RPL) is a critical medical problem in about 0.5-2% of women. The molecular genetic background for spontaneous abortion is being increasingly understood, and some polymorphisms associated with it have been reported. This study investigates alterations of the Bax gene as a pro-apoptotic gene in women with idiopathic RPL. MATERIAL AND METHODS: The frequency of mutations in the Bax gene of 67 idiopathic RPL women was studied in comparison to a sample of 70 healthy women. The promoter and the entire coding regions (exons 1-7) were amplified using polymerase chain reaction (PCR). The purity of the PCR product was first verified by electrophoresis on a 2% agarose gel. The amplified fragment was then sequenced by automated DNA sequencing. RESULTS: A statistically significant difference was observed between patients and the control group regarding the frequency of alleles A(-179)G in the Bax promoter region (p= 0.013). Also among patients, G90C and G95A transitions were found in the coding region of exon 1 that change amino acid glutamine (Q) to histidine (H) and arginine (R) to lysine (K), respectively. A statistically significant association was observed between H allele (p = 0.0001) and K allele (p< 0.0001) and the occurrence of RPL. CONCLUSIONS: Our results indicate an association between A(-179)G mutation in the Bax promoter and RPL. Moreover, two polymorphisms, G90C and G95A in exon 1, found among our patients, could be considered as genetic factors making people susceptible to miscarriages. According to our findings, the Bax gene has an important role in pregnancy loss and the variations of this gene could help in the assessment of RPL.