Effect of THBS1 and P21 Gene Polymorphisms and Their Interaction On Risk of Pre-eclampsia

Abstract

This study aimed to evaluate the association of THBS1 (Thrombospondin 1) and P21 gene polymorphisms and their interaction with the risk of PE. A case-control study was conducted, involving 175 pregnant women with PE and 350 normotensive pregnant women recruited from two tertiary hospitals. Genotyping of 13 single-nucleotide polymorphisms in the THBS1 and P21 genes was performed using the MassArray platform. Univariate and multivariate logistic regression analyses were performed to evaluate the association between THBS1 and P21 gene polymorphisms and risk of PE. Classification and regression tree (CART) analysis was used to identify potential gene-gene interactions, and logistic regression was applied to assess their impact on PE risk. After adjusting for confounding factors, the THBS1 rs2169830 polymorphism was significantly associated with decreased susceptibility to PE (additive model: aOR = 0.12, p = 0.003), while the P21 rs762624 polymorphism was significantly associated with an increased risk of PE (additive model: aOR = 2.24, p = 0.002). CART and logistic regression analyses identified a significant effect of interaction between polymorphisms in rs762624, rs2292305, and rs1478604 on the susceptibility of PE, with individuals carrying the rs762624CC-rs2292305AA/GG-rs1478604TT/CC genotype combination having the highest risk of PE (aOR = 4.533, p < 0.001). Our findings highlight the importance of THBS1 rs2169830 and P21 rs762624 polymorphisms, along with their interaction, in influencing PE risk. The present study provides a foundation for a more profound understanding of the mechanisms underlying PE.

Keywords: P21; THBS1; Gene interaction; Polymorphism; Pre-eclampsia; SNP.