Mendelian Randomization Study of the Relationship Between Serum Matrix Metalloproteinases and the Occurrence of Sepsis

Abstract

Abstract Background Observational studies have shown that matrix metalloproteinases (MMPs) are associated with sepsis. However, it is unknown whether this association represents a causal relationship. Methods Mendelian randomization (MR) analysis was conducted to assess the potential causal role of circulating MMPs in sepsis. Single nucleotide polymorphisms (SNPs) associated with circulating MMPs levels were used as instrumental variables (IVs). In a sepsis genome-wide association study comprising 1573 cases and 454,775 European ancestry controls, we examined these IVs' effects using a two-sample MR study. Causal estimates were calculated using inverse variance weighting (IVW), the weighted median method, and MR-Egger analysis. Results Genetically predict that MMP-1 (OR = 1.011, 95% CI 0.772–1.325, p = 0.936), MMP-3 (OR = 1.036, 95% CI 0.862–1.244, p = 0.707), MMP-7 (OR = 1.206, 95% CI 0.960–1.515, p = 0.108), MMP-8 (OR = 1.041, 95% CI 0.949–1.144, p = 0.395), MMP-9 (OR = 1.101, 95% CI 0.831–1.458, p = 0.503), MMP-10 (OR = 1.028, 95% CI 0.840–1.260, p = 0.789) was not associated with the risk of sepsis. Conclusions The MR study does not provide evidence that circulating levels of MMPs (1, 3, 7, 8, 9, 10) were the causes of sepsis.

Keywords

• Sepsis
• Metalloproteinases (MMPs)
• Mendelian randomization (MR)
• Single nucleotide polymorphisms (SNPs)