C-reactive protein polymorphisms are associated with the cortisol awakening response in basal conditions in human subjects

Abstract

Cortisol affects the acute-phase response, but it is unknown whether C-reactive protein (CRP), an acute-phase reactant, also affects hypothalamus–pituitary–adrenal axis activity. In the present study, associations were explored between CRP haplotypes with plasma CRP concentrations and basal salivary cortisol level. We included 266 physically healthy Caucasian subjects (103 females and 163 males) aged between 18 and 65 years of whom 94 had a psychiatric disorder in a genetic association study. Six tag single-nucleotide polymorphisms capturing the common genetic variation of the CRP gene were genotyped (i.e. rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) to yield common CRP haplotypes. Plasma CRP concentrations, the salivary cortisol awakening response (CAR) (0, 30, 45, and 60 min after awakening), and the diurnal cortisol decline (11:00, 15:00, 19:00, and 23:00 h) were assessed for 2 days. rs2808628, rs1205, rs1417938, and rs3091244 showed expected associations not only with CRP concentrations, but also with salivary cortisol levels during the CAR. Five well-characterized CRP haplotypes were arranged in ascending order according to increasing CRP levels. There was an inverse linear association between CRP haplotypes and cortisol levels during the CAR, but no association with the diurnal cortisol decline. Hence, genetic variants in the CRP gene that are associated with lifetime plasma CRP levels were also associated with salivary cortisol levels after awakening, in basal, non-inflammatory conditions.

Keywords::

• Acute-phase response
• C-reactive protein
• hypothalamic–pituitary–adrenal axis
• Mendelian randomization
• polymorphisms
• salivary cortisol

Acknowledgements

The authors thank Prof. Dr P.E. Slagboom and Dr H.E.D. Suchiman of the Molecular Epidemiology Section for SNP genotyping and their valuable comments. Dr N. van Leeuwen of the Division of Medical Pharmacology/LACDR is thanked for DNA isolation and her assistance with genotyping.

Funding: The funding for this study was provided by the Leiden University Medical Center (LUMC) and Rivierduinen Mental Health Center. Part of this study was funded by a grant from the Netherlands Brain Foundation (Hersenstichting Nederland, Grant No. 15F07(2).24).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.