A genome‐wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain. (26th June 2014)

• Record Type: Journal Article
• Authors: Meng, W.; Deshmukh, H.A.; van Zuydam, N.R.; Liu, Y.; Donnelly, L.A.; Zhou, K.; Wellcome Trust Case Control Consortium 2 (WTCCC2); Surrogate Markers for Micro‐ and Macro‐Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group; Morris, A.D.; Colhoun, H.M.; Palmer, C.N.A.; Smith, B.H.
• Is Part Of: European journal of pain. Volume 19:Number 3(2015)
• Page Start: 392
• Page End: 399
• Publication Date: 2014-06-26
• Subjects: Pain -- Periodicals; Pain -- Treatment -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1002/ejp.560
• Languages: English
• ISSNs: 1090-3801

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="ejp560-sec-0001" sec-type="section"> <title>Background</title> <p>Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.</p> </sec> <sec id="ejp560-sec-0002" sec-type="section"> <title>Method</title> <p>We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non‐genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.</p> </sec> <sec id="ejp560-sec-0003" sec-type="section"> <title>Results</title> <p>After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to <italic>GFRA2</italic> with a lowest <italic>p</italic>‐value of 1.77 × 10<sup>−7</sup> at rs17428041. The narrow‐sense heritability of this phenotype was 11.00%.</p> </sec> <sec id="ejp560-sec-0004" sec-type="section"> <title>Conclusion</title> <p>This genome‐wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near <italic>GFRA2</italic> with the disorder, which needs to be verified in an independent cohort and at the molecular level.</p> </sec> </abstract>