Association of Plasminogen Activator Inhibitor-1 4G/5G and Angiotensin Converting Enzyme I/D Polymorphisms with Recurrent Spontaneous Abortion in Sudanese Women

Abstract

This was retrospective analytical case control study aimed to investigate the relationship between recurrent abortion and common polymorphisms in PAI-1 4G/5G and ACE I/D genes polymorphisms, in sudanese women those visited Omdurman Maternatiy Hospital for obscitetric followup and health care during the period of Fep 2019 to Dec 2019. A total of 125 subject were involved in this study, 64 women with recurrent abortions (at least three times); of unknown cause were selected as cases and 61 healthy women with two or more normal term deliveries and without a history of abortion as controls matched age. 5 ml EDTA blood samples were collected from patients and controls and the data were collected from questionnaires showed demographic, personal and family history information. The total genomic DNA were isolated from blood leukocytes by GF-1 Blood DNA extraction kit, and the status of the PAI-1 4G/5G and ACE I/D polymorphisms were determined by conventional Polymerase chain reaction technique. The data were analyzed using SPSS version 24. The study results showed that the homozygosity for ACE D/D polymorphism (mutant type) detected in 59 cases (92.2%), and 38 controls (62.3%) (p-value 0.000*) and the frequency of D allele was 123(96.1) also significant (p-value 0.000*) so patients with homozygote genotype were significantly more prone to recurrent pregnancy loss in contrast to control group. No one from the recurrent miscarriage group, were homozygote (I/I) (wild type) for ACE polymorphism. The result of PAI-1 4G/4G polymorphisms (mutant type) showed significant variations among patients compared to the control groups (p value 0.00). The combination of both PAI-1 4G/5G and ACE I/D polymorphisms, showed that the combination of ACE D/D and PAI-1 4G/4G hypofibrinolytic polymorphisms were significant (p-value 0.000*), also the combination of ACE D/D and PAI-1 4G/5G rsult was highly significantly different (52.6% for RM cases versus 44.1 for controls (p-value 0.000*). No significant association were found between these genes polymorphisms and time of abortion in cases (p-value >0.05). In conclusion, these two genes polymorphisms could be a thrombophilic variant leading to abortion, analysis of these mutations and other susceptibility factors are recommended in patients with recurrent abortion.