The association of the placental CASPASE-3 gene polymorphisms and preeclampsia susceptibility and in-silico analysis

Preeclampsia is a pathologic complication of pregnancy, associated with increased apoptosis in the cytotrophoblasts as the main cause of this disorder. Caspase-3 is a key apoptosis-related enzyme that both mitochondrial and death receptor apoptotic pathways can activate. In this study, we aimed to investigate the effect of placental CASP-3 rs4647602 and rs4647610 polymorphisms on PE susceptibility. The placentas of 106 PE women and 115 normotensive pregnant women were collected. Genomic DNA was extracted from the placenta. For genotyping of CASP-3 rs4647602 and rs4647610 polymorphisms, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used. The frequencies of placental CASP-3rs4647602CA and rs4647610GA genotypes were higher in PE women; however, the differences were not statistically different (P=0.36 and P=0.13, respectively). In addition, the frequencies of CA-GA combined genotypes and A-A haplotype were higher in PE women compared to the control women; however, the differences were marginally non-significant (P=0.051 and P=0.08, respectively). In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings.