Genetic and psychological factors interact to predict physical impairment phenotypes following exercise-induced shoulder injury

Abstract

Paul A Borsa,1 Jeffrey J Parr,2 Margaret R Wallace,3 Samuel S Wu,4 Yunfeng Dai,4 Roger B Fillingim,5 Steven Z George6 1Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA; 2School of Health Professions, University of Southern Mississippi, Hattiesburg, MS, USA; 3Department of Molecular Genetics and Microbiology, Center for Epigenetics, UF Genetics Institute, University of Florida, Gainesville, FL, USA; 4Department of Biostatistics, University of Florida, Gainesville, FL, USA; 5Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA; 6Duke Clinical Research Institute and Department of Orthopaedic Surgery, Duke University, Durham, NC, USABackground: We investigated interactions between genetic and psychological factors in predicting shoulder impairment phenotypes. We hypothesized that pro-inflammatory genes would display stronger relationships compared with pain-related genes when combined with psychological factors for predicting phenotypic changes.Subjects and methods: Altogether, 190 participants completed a 5-day experimental protocol. An experimental shoulder injury model was used to induce physical impairment, and a priori selected genetic (pain-related, pro-inflammatory) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as predictors of interest. Impairment phenotypes were injury-induced deficits in range of motion (ROM) and strength. After controlling for age, sex, and race, genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each phenotype.Results: Strong statistical evidence was provided for interactions between: 1) IL-1β (rs1143634) and fear of pain for predicting loss of shoulder flexion and abduction, 2) IL-1β (rs1143634) and anxiety for predicting loss of flexion, and 3) IL-1β (rs1143634) and depressive symptoms for predicting loss of internal rotation. In addition, the interaction between OPRM1 (rs1799971) and fear of pain as well as COMT (rs4818) and pain catastrophizing provided strong statistical evidence for predicting strength loss.Conclusion: Pro-inflammatory gene variants contributed more to physical impairment with two single nucleotide polymorphisms (SNPs; IL-1β [rs1143634] and TNF/LTA [rs2229094]) interacting with psychological factors to predict six shoulder impairment phenotypes. In comparison, two pain-related gene SNPs (OPRM1 [rs1799971] and COMT [rs4818]) interacted with psychological factors to predict four shoulder impairment phenotypes (abduction: 5-day average loss; strength loss: 5-day average, peak, and relative loss). Keywords: single nucleotide polymorphisms, inflammation, IL-1β, fear of pain, pain catastrophizing

Keywords

• single nucleotide polymorphisms
• inflammation
• IL-1β
• fear of pain
• pain catastrophizing