Association of IL‐35 Subunits, IL‐12A rs568408 and EBI3 rs4740, Gene Polymorphisms With Preeclampsia Risk

Preeclampsia (PE) is a major pregnancy complication with considerable maternal and fetal morbidities. The recent evidence indicates that immunological factors have critical roles in PE pathogenesis. This study assessed the association between genetic variations in IL-35 components, specifically IL-12A (rs568408) and EBI3 (rs4740) polymorphisms, and PE susceptibility in an Iranian population. A case-control study with 470 participants was carried out, and polymorphism detection was achieved by the PCR-RFLP technique. Genetic analysis revealed distinct associations between IL-35 components polymorphisms and PE risk. For IL-12A rs568408, the AA mutant genotype significantly increased PE susceptibility (OR = 3.350, p = 0.007), with stronger associations in severe PE cases (OR = 5.048, p < 0.001). Similarly, the mutant allele showed risky effects in total group and severe subgroup (OR = 1.743, p = 0.001; OR = 2.307, p < 0.001). The EBI3 rs4740 polymorphism analysis showed that AA genotype carriers had a protective effect (OR = 0.495, p = 0.036), particularly noticeable in severe cases (OR = 0.409, p = 0.037). In addition, the mutant allele demonstrated protective effects in the total PE, severe and particularly in early-onset manifestations (OR = 0.651, OR = 0.559, OR = 0.478, respectively). Combined genotype analysis showed that IL-12A AA/EBI3 GA carriers had the highest risk of severe, early-onset PE (OR = 5.280, p = 0.046, OR = 5.945, p = 0.038). This study provides a better understanding of the causes of PE and points out possible genetic markers to be used in its risk assessment.