Table 2.
Genes implicated in human musculoskeletal pain conditions
| Gene or genetic region | Disease | Associated intermediate phenotype |
|---|---|---|
| ADRB2 (β2 adrenergic receptor) | Fibromyalgia93,121 CWP92 TMD122 |
Psychological distress;122 blood pressure;122 sleep dysfunction in fibromyalgia;93 low PBMC basal and isoproterenol-stimulated cAMP levels93 |
| COMT (Catechol O-methyltransferase) | Fibromyalgia85–90 TMD16 |
In fibromyalgia: pain catastrophizing;123 increased pain level during elevated pain attention;123 thermal and pressure pain sensitivity;90 psychological distress;109 increase number of tender points in TPC;89 pain and positive affect interaction;124 and FIQ-defined pain, fatigue, sleep disturbance, morning stiffness and disability85,88 In LBP: altered cortical pain processing,108 increased pain intensity,125 less favourable treatment outcome125–127 In TMD: interaction with orthodontic treatment128 and reduced efficacy of propranolol treatment of TMD;118 experimental pain sensitivity16 |
| HLA/MHC region | Fibromyalgia103,104,129 | NA |
| HTR2A (5-hydroxytryptamine receptor 2A, also known as serotonin receptor 2A) | Fibromyalgia100,101 TMD102 |
Tender point count100 and pain intensity in fibromyalgia;110 increased somatic symptom counts;130 reduced perception of environmental quality;101 increased in SCL-90-R total score and subscales scores for somatic awareness, anxiety, psychosis, obsessive–compulsive behaviour, hostility, global severity index, interpersonal sensitivity, phobic anxiety, depression110 |
| SERPINA1 (α1-antitrypsin) | Fibromyalgia106,107 CWP130 |
‘Intense creative energy’ risk phenotype;107 increased number of painful body sites130 |
| SLC6A4 (sodium-dependent serotonin transporter) | Fibromyalgia95–97 TMD98,99 |
Higher BDI and SCL-90-R scores;95 SCL-90 scores for somatic awareness and anger;99 TPQ harm avoidance trait;96 increased salivary cortisol level;97 increased leukocyte count97 |
Abbreviations: BDI, Beck Depression Inventory; CWP, chronic widespread pain; FIQ, Fibromyalgia Impact Questionnaire; LBP, low back pain; NA, not assessed; PBMC, peripheral blood mononuclear cell; SCL-90, Symptom Checklist-90; SCL-90-R, SCL-90-Revised; TMD, temporomandibular joint disorders; TPC, tender point count; TPQ, Tridimensional Personality Questionnaire.