The combined impact of persistent infections and human genetic variation on C-reactive protein levels

Multiple human pathogens establish chronic, sometimes life-long infections. Even if they are often latent, these infections can trigger some degree of local or systemic immune response, resulting in chronic low-grade inflammation. There remains an incomplete understanding of the potential contribution of both persistent infections and human genetic variation on chronic low-grade inflammation. We searched for potential associations between seropositivity for 13 persistent pathogens and the plasma levels of the inflammatory biomarker C-reactive protein (CRP), using data collected in the context of the UK Biobank and the CoLaus|PsyCoLaus Study, two large population-based cohorts. We performed backward stepwise regression starting with the following potential predictors: serostatus for each pathogen, polygenic risk score for CRP, as well as demographic and clinical factors known to be associated with CRP. We found evidence for an association between Chlamydia trachomatis (P-value = 5.04e-3) and Helicobacter pylori (P-value = 8.63e-4) seropositivity and higher plasma levels of CRP. We also found an association between pathogen burden and CRP levels (P-value = 4.12e-4). These results improve our understanding of the relationship between persistent infections and chronic inflammation, an important determinant of long-term morbidity in humans.