Causal Relationship Between Inflammation and Preeclampsia: Genetic Evidence from a Mendelian Randomization Study

Preeclampsia (PE) is a hypertensive disorder of pregnancy. PE patients were reported to have higher serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) than those in healthy controls. However, whether the expressions of these inflammation biomarkers have a causal relationship with PE is unspecified. We applied the Mendelian randomization method to infer the causal relationship between inflammation biomarkers (e.g., CRP, IL-6, interleukin 1 receptor antagonist [IL-1ra] and TNF-α) and PE. Single nucleotide polymorphisms (SNPs) strongly related to inflammation biomarkers were used as instrumental variables. CRP, IL-1ra and IL-6 levels showed no significant effect on PE progression, while the genetic predicted higher level of TNF-α significantly increased the risk of PE (OR per 1-SD increase in TNF-α: 4.33; 95% CI [1.99, 9.39]; p = .00021). The findings suggest that pro-inflammatory activity of TNF-α could be a determinant for PE progression. More antenatal care should be given to those pregnant women with higher level of inflammation biomarkers, especially TNF-α.