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 article

98 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

Fingerprint

Neuralgia
Meta-Analysis
HLA-A Antigens
Genes
HLA-DRB1 Chains
HLA-B Antigens
Genome-Wide Association Study
Synaptic Transmission
Chronic Pain
Interleukin-6
Health

Keywords

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

Cite this

@article{9584ae7f840e42a588a241eb8d5e61a3,
title = "Systematic review and meta-analysis of genetic risk factors for neuropathic pain",
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.",
keywords = "Neuropathic pain, Genetic risk factor, Polymorphisms, Genome-wide association studies, Candidate gene association studies, Systematic review, Meta-analysis",
author = "Abirami Veluchamy and H{\'e}bert, {Harry L.} and Weihua Meng and Palmer, {Colin N. A.} and Smith, {Blair H.}",
note = "This work was supported by the DOLORisk consortium which is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No: 633491. B.H.S. is a member of the DOLORisk consortium and is partly supported by this grant. He has received, on behalf of his institution, occasional lecture and consultancy fees from Pfizer Ltd, Napp Pharmaceuticals, Grunenthal and Eli Lilly. C.N.A.P is also partly supported by DOLORisk as well as by the National Institute of Health Research (UK). H.L.H. and A.V. are supported by DOLORisk. W.M declares no conflict of interest. The grant reference number is 633491-DOLORisk-RIA from EU Horizon 2020-PHC1-2014.",
year = "2018",
month = "5",
doi = "10.1097/j.pain.0000000000001164",
language = "English",
volume = "159",
pages = "825--848",
journal = "Pain",
issn = "0304-3959",
publisher = "Lippincott, Williams & Wilkins",
number = "5",

}

Systematic review and meta-analysis of genetic risk factors for neuropathic pain. / Veluchamy, Abirami; Hébert, Harry L.; Meng, Weihua; Palmer, Colin N. A.; Smith, Blair H. (Lead / Corresponding author).

In: Pain, Vol. 159, No. 5, 05.2018, p. 825-848.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Systematic review and meta-analysis of genetic risk factors for neuropathic pain

AU - Veluchamy, Abirami

AU - Hébert, Harry L.

AU - Meng, Weihua

AU - Palmer, Colin N. A.

AU - Smith, Blair H.

N1 - This work was supported by the DOLORisk consortium which is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No: 633491. B.H.S. is a member of the DOLORisk consortium and is partly supported by this grant. He has received, on behalf of his institution, occasional lecture and consultancy fees from Pfizer Ltd, Napp Pharmaceuticals, Grunenthal and Eli Lilly. C.N.A.P is also partly supported by DOLORisk as well as by the National Institute of Health Research (UK). H.L.H. and A.V. are supported by DOLORisk. W.M declares no conflict of interest. The grant reference number is 633491-DOLORisk-RIA from EU Horizon 2020-PHC1-2014.

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

KW - Neuropathic pain

KW - Genetic risk factor

KW - Polymorphisms

KW - Genome-wide association studies

KW - Candidate gene association studies

KW - Systematic review

KW - Meta-analysis

U2 - 10.1097/j.pain.0000000000001164

DO - 10.1097/j.pain.0000000000001164

M3 - Review article

VL - 159

SP - 825

EP - 848

JO - Pain

JF - Pain

SN - 0304-3959

IS - 5

ER -