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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.
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2013 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 154, no 3, p. 427-33, article id S0304-3959(12)00648-3Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2013. Vol. 154, no 3, p. 427-33, article id S0304-3959(12)00648-3
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:mau:diva-33169DOI: 10.1016/j.pain.2012.12.003ISI: 000315299800017PubMedID: 23318129Scopus ID: 2-s2.0-84874526454OAI: oai:DiVA.org:mau-33169DiVA, id: diva2:1495028
Available from: 2020-11-04 Created: 2020-11-04 Last updated: 2024-02-05Bibliographically approved
In thesis
1. Multiplex HLA-DR-DQ genotyping: for genetic epidemiology and clinical risk assessment
Open this publication in new window or tab >>Multiplex HLA-DR-DQ genotyping: for genetic epidemiology and clinical risk assessment
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The human leukocyte antigens (HLA) are highly polymorphic cell surface proteins encoded in the major histocompatibility complex (MHC) region on chromosome 6. The HLA system has been well known as transplantation antigens but the primary biological role of the HLA molecules is regulation of immune response by presenting peptide fragments to T-lymphocytes. As regulators of immune responses the HLA molecules are also of importance for susceptibility to several autoimmune and inflammatory diseases. Genotyping of these loci is therefore significant in research targeting the mechanisms of HLA associated diseases, in exploring new epidemiological associations between HLA and specific disease, and as a clinical tool for risk assessment for diseases with well defined associations. Although several commercial HLA genotyping methods are available, many require multiple steps, have low throughput and high cost. The aim of the work within this dissertation was to develop a robust, costeffective method for HLA-DRB1, -DQA1 and -DQB1 genotyping suitable for use in an epidemiological context and clinical investigation. The method was optimized with specific focus on risk alleles for type 1 diabetes mellitus and celiac disease, two autoimmune disorders with significant impact on public health. By combining PCR with sequence specific primers (PCR-SSP), product separation by capillary gel electrophoresis and fluorescence detection in the developed method, all three loci could be analyzed in a single step, resulting in low reagent cost and fast turnaround time. This in combination with the low total consumption of DNA template allows the method to be used in epidemiological studies. 10 A simplified version of the developed method is currently used for clinical risk assessment for celiac disease when histological and/or serologic results are ambiguous in investigated subjects or when a gluten-free diet has been initiated before diagnostic tests have been performed. The low cost of this newly developed method has enabled HLA typing as a tool in screening programs for high-risk groups, such as individuals with Down syndrome or type 1 diabetes, to preclude the risk for celiac disease and thus avoid periodic screening for auto-antibodies. This method is also used to analyze samples from children all over Sweden with newly diagnosed diabetes in the Better Diabetes Diagnosis project. The developed method was also used in two explorative association studies not related to type 1 diabetes or celiac disease. In one study the association between HLA-DRB1, -DQA1 and -DQB1 and acute myocardial infarction was investigated showing only weak associations. In the second study the HLA-DR-DQ haplotype effect on developing chronic pain after inguinal hernia surgery was explored demonstrating an HLA dependent risk of developing pain

Place, publisher, year, edition, pages
Malmö University. Faculty of Health and Society, 2012. p. 53
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2012:3
Keywords
HLA-DRB1, HLA-DQB1, HLA-DQA1, PCR-SSP, type 1 diabetes, celiac disease, autoimmune disease, capillary gel electrophoresis, genotyping
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:mau:diva-7337 (URN)13570 (Local ID)978-91-7104-431-0 (ISBN)13570 (Archive number)13570 (OAI)
Note

Note: The papers are not included in the fulltext online.

Paper IV in dissertation as manuscript with title "The DRB1*04-DQB1*03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery."

Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2024-03-05Bibliographically approved

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