Systematic review and meta-analysis of genetic risk factors for neuropathic pain

Abirami Veluchamy, Harry L. Hébert, Weihua Meng, Colin N. A. Palmer, Blair H. Smith (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

16 Citations (Scopus)
284 Downloads (Pure)

Abstract

Neuropathic pain (NP) is an increasingly common chronic pain state and a major health burden, affecting approximately 7-10% of the general population. Emerging evidence suggests that genetic factors could partially explain individual susceptibility to NP and the estimated heritability in twins is 37%. The aim of this study was to systematically review and summarize the studies in humans that have investigated the influence of genetic factors associated with NP. We conducted a comprehensive literature search and performed meta-analyses of all the potential genetic variants associated with NP. We reviewed 29 full-text articles and identified 28 genes that were significantly associated with NP, mainly involved in neurotransmission, immune response, and metabolism. Genetic variants in HLA genes, COMT, OPRM1, TNFA, IL6, and GCH1, were found to have an association with NP in more than one study. In the meta-analysis, polymorphisms in HLA-DRB1*13 (OR,2.96; CI,1.93-4.56), HLADRB1*04 (OR,1.40; CI, 1.02-1.93), HLA-DQB1*03 (OR,2.86; CI,1.57-5.21), HLA-A*33 (OR,2.32; CI,1.42-3.80), and HLA-B*44 (OR,3.17; CI,2.22-4.55) were associated with significantly increased risk of developing NP whereas HLA-A*02 (OR,0.64; CI,0.47- 0.87) conferred reduced risk and neither rs1799971 in OPRM1 (OR, 0.55; CI, 0.27- 1.11) nor rs4680 in COMT (OR, 0.95; CI, 0.81-1.13) were significantly associated with NP. These findings demonstrate an important and specific contribution of genetic factors to the risk of developing NP. However, large-scale replication studies are required to validate these candidate genes. Our review also highlights the need for genome-wide association studies with consistent case definition to elucidate the genetic architecture underpinning NP.
Original languageEnglish
Pages (from-to)825-848
Number of pages24
JournalPain
Volume159
Issue number5
Early online date18 Jan 2018
DOIs
Publication statusPublished - May 2018

Keywords

  • Neuropathic pain
  • Genetic risk factor
  • Polymorphisms
  • Genome-wide association studies
  • Candidate gene association studies
  • Systematic review
  • Meta-analysis

Fingerprint Dive into the research topics of 'Systematic review and meta-analysis of genetic risk factors for neuropathic pain'. Together they form a unique fingerprint.

Cite this