Single nucleotide polymorphism (SNP) rs3751143 in P2RX7 is associated with therapy failure in chronic Q fever while rs7125062 in MMP1 is associated with fewer complications

Abstract Objectives Chronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nuclear polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). In the current study we evaluated the association of SNPs in these innate immunity and MMP genes with clinical outcomes. Methods SNPs were selected from previous association studies and analyzed in a cohort of patients with chronic Q fever. The primary outcome was all-cause mortality; secondary outcomes were therapy failure and chronic Q fever-related complications. Subdistribution hazard ratios (SHR) were calculated. Results Nineteen SNPs were analyzed in 134 patients with proven and 29 with probable chronic Q fever. In multivariable analysis, none of the selected SNPs were associated with all-cause mortality. However, SNP rs3751143 located in P2RX7 appeared to be associated with therapy failure (SHR 2.42 (95% CI, 1.16-5.05), p=0.02) which is in line with other reports, showing that a loss-of-function of the P2X7-receptor leads to inefficient killing of intracellular organisms. In addition, SNP rs7125062 located in MMP1, involved in the cleavage of extracellular matrix, was associated with fewer chronic Q fever-related complications such as acute aneurysms (SHR 0.49 (95% CI, 0.29-0.83), p=0.008). Conclusions A polymorphism in P2RX7, known to lead to loss-of-function of the receptor and inefficient killing of intracellular organisms, and a polymorphism in MMP1 were associated with more therapy failure and fewer complications as acute aneurysms in patients with chronic Q fever, respectively.