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The DQB1*03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation

Dominguez, Cecilia A.a,*; Kalliomäki, Maijab,c; Gunnarsson, Ulfd; Moen, Aurorae,f; Sandblom, Gabrield; Kockum, Ingrida; Lavant, Ewag; Olsson, Tomasa; Nyberg, Fredh; Rygh, Lars Jørgeni; Røe, Ceciliej; Gjerstad, Johannese,f,1; Gordh, Torstenb,1; Piehl, Fredrika,1

doi: 10.1016/j.pain.2012.12.003
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Summary There is a human leukocyte antigen-dependent risk of developing neuropathic pain after inguinal surgery and it is mediated by the DRB1*04-DQB1*03:02 haplotype.

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.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

aNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

bDepartment of Surgical Sciences, Anaesthesiology/Pain research, Uppsala University, Uppsala, Sweden

cDepartment of Anaesthesiology, University of Tammerfors, Tampere, Finland

dDepartment of Clinical Science, Intervention and Technology (Surgery), Karolinska Institutet, Huddinge, Sweden

eNational Institute of Occupational Health, Oslo, Norway

fDepartment of Molecular Biosciences, University of Oslo, Norway

gDepartment of Biomedical Laboratory Science, Faculty of Health and Society, Malmö University/Labmedicine Skåne, Clinical Chemistry, Malmö, Sweden

hDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

iDepartment of Anesthesiology and Intensive Care, Haukeland University Hospital, Bergen, Norway

jDepartment of Physical Medicine and Rehabilitation, Oslo University Hospital, Ullevaal, Norway

*Corresponding author. Address: Neuroimmunology Unit, CMM L8:05, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Tel.: +46 8 51776041; fax: +46 8 51770885.

E-mail: cecilia.dominguez@ki.se

1These authors contributed equally to this work.

Submitted March 7, 2012; revised October 30, 2012; accepted December 4, 2012.

© 2013 Lippincott Williams & Wilkins, Inc.
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