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

Twin Res Hum Genet. 2023 Jun;26(3):231-235. doi: 10.1017/thg.2023.27. Epub 2023 Jul 17.

Abstract

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.

Keywords: Mendelian randomization method; Preeclampsia; TNF-α; inflammation.

MeSH terms

  • Biomarkers
  • C-Reactive Protein / genetics
  • Female
  • Humans
  • Inflammation / genetics
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin-6* / genetics
  • Mendelian Randomization Analysis
  • Pre-Eclampsia* / genetics
  • Pre-Eclampsia* / metabolism
  • Pregnancy
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin 1 Receptor Antagonist Protein
  • C-Reactive Protein
  • Biomarkers