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

Paul A Borsa, Jeffrey J Parr, Margaret R Wallace, Samuel S Wu, Yunfeng Dai, Roger B Fillingim, Steven Z George, Paul A Borsa, Jeffrey J Parr, Margaret R Wallace, Samuel S Wu, Yunfeng Dai, Roger B Fillingim, Steven Z George

Abstract

Background: 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: IL-1β; fear of pain; inflammation; pain catastrophizing; single nucleotide polymorphisms.

Conflict of interest statement

Disclosure The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) The interaction between IL-1β (rs1143634) and FPQ demonstrated strong statistical evidence for predicting 5-day average loss of active shoulder flexion associated with exercise-induced injury. (B) The interaction between IL-1β (rs1143634) and STAI demonstrated strong statistical evidence for predicting loss of peak flexion associated with exercise-induced injury. Abbreviations: Avg., average; FPQ, Fear of Pain Questionnaire; ROM, range of motion; STAI, State-Trait Anxiety Inventory.
Figure 2
Figure 2
(A) The interaction between IL-1β (rs1143634) and FPQ demonstrated strong statistical evidence for predicting loss of 5-day average abduction associated with exercise-induced injury. (B) The interaction between IL-1β (rs1143634) and FPQ demonstrated strong statistical evidence for predicting loss of peak abduction associated with exercise-induced injury. Abbreviations: FPQ, Fear of Pain Questionnaire; ROM, range of motion.
Figure 3
Figure 3
Interaction of genetic (IL-1β rs1143634) and psychological (PHQ) factors for peak loss of internal rotation ROM. Abbreviations: PHQ, Patient Health Questionnaire; ROM, range of motion.
Figure 4
Figure 4
(A) The interaction between OPRM1 (rs1799971) and FPQ demonstrated strong statistical evidence for predicting 5-day average post-exercise MVIC impairment phenotype. (B) The interaction between OPRM1 (rs1799971) and FPQ also demonstrated strong statistical evidence for predicting peak post-exercise MVIC impairment phenotype. Abbreviations: Avg., average; FPQ, Fear of Pain Questionnaire; MVIC, maximal voluntary isometric contraction; ROM, range of motion.

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