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

Abstract

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, and 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.

Common infections and neuroimaging markers of dementia in three UK cohort studies

“…Neurotropic pathogens—such as herpes simplex virus (HSV)—are able to directly infect cells in the central nervous system, possibly triggering amyloid beta (Aβ) pathology, 3 , 4 neuroinflammation, and neuronal loss. 5 Infection or cumulative infection burden could additionally drive systemic changes, including inflammation, 6 which have been implicated in dementia etiology. 7 , 8 Nevertheless, previous studies have primarily focused on a few hypothesis‐driven pathogens or pathogen families, and findings have been mixed.…”