Association between the Ile164 2 Adrenergic Receptor Polymorphism and Fatigue in Patients with Rheumatoid Arthritis

Introduction: In the present work, the frequency of inherited polymorphisms of the beta 2 adrenergic receptor (beta 2AR) gene and their association with fatigue in patients with rheumatoid arthritis (RA) was examined. Methods: An allele-specific polymerase chain reaction was used to determine the common variants of the beta 2AR at position 16, 27, and 164 in 92 German RA outpatients. Health Assessment Questionnaire (HAQ-DI), Beck Depression Inventory (BDI), Perceived Stress Questionnaire (PSQ-30), Multidimensional Fatigue Inventory (MFI-20) were utilized. Results: 34.7% of German RA patients were diagnosed with associated fatigue. Fatigued patients were more likely to carry the Ile allele at position 164 (OR 7.33, 95% CI 1.09-59.8, p = 0.049). Comparing these risk factors' contribution to different fatigue dimensions revealed that Ile164 carriers only had significantly higher MFI-20 mean values for general fatigue (p = 0.014) while the clinical difference among other MFI subscales was the largest for mental fatigue (carrier: 8.23, SD: 4.22, noncarrier: 5.67, SD: 1.56, p = 0.089, Cohen's d = 0.629). Disease activity, perceived stress, and depression were also associated with fatigue with higher mean values for DAS28CRP (p = 0.038), PSQ (p < 0.001), and BDI-II (p < 0.001) in fatigued patients. Physical fatigue was correlated with disease activity (p = 0.009) and depression (p = 0.001) while mental fatigue showed associations with depression (p = 0.001) and perceived stress (p = 0.028). Conclusion: The discovery study indicates that the Ile164 polymorphism might in contrast to other beta 2AR polymorphisms affect fatigue levels in RA patients. This association was observed especially with mental fatigue. Further replication studies are warranted to determine further role of beta 2AR polymorphisms in RA patients.