O-47: Molecular Study of Internal ApoptoticPathway BAX and BCL2 Genes and MitochondrialGenome in Idiopathic Repeated PregnancyLoss

Background: Pregnancy is the process from the fertilized ovum to the fetus with capability of extra uterine survival. Pregnancy loss is the most common complication of pregnancies. Advances in the detection of early pregnancy revealed that about 70% of human conceptions fail to achieve viability but clinically recognized pregnancies terminate as a miscarriage in about 15% of cases. About 1 in 300 couples and 0.5-2% of women are involved in repeated pregnancy loss (RPL). Various etiological factors involve in RPL and the main part of them remains unknown. Among them the genetic factors are important. The apoptotic changes and the aberrant expression of many genes including apoptotic related genes were seen in RPL. Materials and Methods: Familial pedigrees of 335 consecutive couples suffering from RPL were initially evaluated at a primary stage. Among them, 96 women were screened as idiopathic at reproductive age. Molecular genetic variations in internal apoptotic related genes BAX, BCL2 and mitochondrial genome were investigated in comparison to control group. The methods were PCR-SSCP, PCR-Digestion-SSCP, Multiplex PCR and PCR-Direct sequencing. Results: The evaluation of familial pedigree of 335 RPL couples showed 120 cases of RPL in female relatives and 76 cases in male relatives. Other families with RPL were seen in two or three consecutive generations in 15.6% of female relatives. At least two cases of RPL in other consanguineous marriages were observed in 4.2%. There were familial marriages in 51.6% of RPL women and 21.8% of control group (p=0.0003). A statistically significant association was observed between the study and the control groupswith regard to the frequency of alleles A to G (97.76% in RPL and 90.71% in control group) at nucleotide -179 in Bax promoter region (p=0.013). G90C and G95A transitions were found in the coding region of exon 1that 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