title: The DQB1 *03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation.
abstract: Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1*04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1*03:02 allele together with DRB1*04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n=258), where carriers of the DQB1*03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1*04 - DQB1*03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms.
authors: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Department of Surgical Sciences, Anaesthesiology/Pain research, Uppsala University, Uppsala, Sweden Department of Anaesthesiology, University of Tammerfors, Tampere, Finland Department of Clinical Science, Intervention and Technology (Surgery), Karolinska Institutet, Huddinge, Sweden National Institute of Occupational Health, Oslo, Norway Department of Molecular Biosciences, University of Oslo, Norway Department of Biomedical Laboratory Science, Faculty of Health and Society, Malmö University/Labmedicine Skåne, Clinical Chemistry, Malmö, Sweden Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden Department of Anesthesiology and Intensive Care, Haukeland University Hospital, Bergen, Norway Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Ullevaal, Norway.
authors: Cecilia A
authors: CA
authors: Dominguez
authors: Maija
authors: M
authors: Kalliomäki
authors: Ulf
authors: U
authors: Gunnarsson
authors: Aurora
authors: A
authors: Moen
authors: Gabriel
authors: G
authors: Sandblom
authors: Ingrid
authors: I
authors: Kockum
authors: Ewa
authors: E
authors: Lavant
authors: Tomas
authors: T
authors: Olsson
authors: Fred
authors: F
authors: Nyberg
authors: Lars Jørgen
authors: LJ
authors: Rygh
authors: Cecilie
authors: C
authors: Røe
authors: Johannes
authors: J
authors: Gjerstad
authors: Torsten
authors: T
authors: Gordh
authors: Fredrik
authors: F
authors: Piehl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D059350:Chronic Pain / Q000209:etiology / Q000235:genetics*; D017586:Diskectomy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006552:Hernia, Inguinal / Q000503:physiopathology / Q000601:surgery*; D059685:Herniorrhaphy; D006801:Humans; D007405:Intervertebral Disc Displacement / Q000503:physiopathology / Q000601:surgery*; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000209:etiology / Q000235:genetics*; D010149:Postoperative Pain / Q000209:etiology / Q000235:genetics*; D059348:Peripheral Nerve Injuries / Q000209:etiology / Q000235:genetics; D012306:Risk; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen