The Effects of PON1 (Q192R, rs662) Gene Polymorphism, Heavy metals and Oxidative Stress on Risk of Recurrent Spontaneous Abortion in Samples of Iraqi Women

Recurrent spontaneous abortion (RSA) is defined as the occurrence of two or more spontaneous pregnancy losses before reaching the midpoint of gestation. Oxidative stress plays a pivotal role in the pathogenesis of RSA, serving as a key factor in its underlying causes. This research aims to investigate the connection between the Q192R polymorphisms identified in the PON1 gene, responsible for encoding an antioxidant enzyme and the vulnerability to RSA. Paraoxonase 1 (PON1) is a critical enzyme in the body's antioxidant defence system, safeguarding cells against damage caused by reactive oxygen species and heavy metal concentrations that affect pregnancy. The most prevalent PON1 polymorphism is Q192R (rs662), known to influence the antioxidant activity and power of the PON1 enzyme. In this research, blood samples were collected from two groups: 50 women with RSA and 50 women who were apparently in good health. Following DNA extraction, high-resolution melting (HRM) analysis was used to identify the studied SNP; Elisa was used to determine DNA damage and MDA concentrations in serum and heavy metals were determined by a Graphite Furnace-Atomic Absorption Spectrophotometer (GFAAS). The results of this study showed significantly higher levels of 8-OHdG, MDA, arsenic and lead in serum in RSA patients than in apparently healthy women. The genotype findings indicated that the prevalence of the QR (AG) genotype in women experiencing recurrent spontaneous abortion was notably greater than that in seemingly healthy women (74% compared to 16%, respectively, with an odds ratio of 27.2). The values of allele frequency for the A allele were 0.76 and 0.51 for apparently healthy women and women with recurrent spontaneous abortion respectively. The G allele frequency was 0.24 and 0.49 for apparently healthy women and women with recurrent spontaneous abortion respectively. The heterozygous QR genotype is related to the risk of RSA and the minor allele (G allele) is increased in women with RSA.