title: Association of functional variations in COMT and GCH1 genes with postherniotomy pain and related impairment.
abstract: Persistent postoperative pain is a well-established clinical problem with potential severe personal and socioeconomic implications. The prevalence of persistent pain varies across surgery types. Severe persistent pain and related impairment occur in 5% to 10% of patients after groin hernia repair. The substantial interindividual variability in pain-related phenotypes within each surgery type cannot be explained by environmental factors alone, suggesting that genetic variation may play a role. We investigated the contribution of COMT and GCH1 to persistent postherniotomy pain (PPP)-related functional impairment. Prospective data from 429 Caucasian male patients with hernia were collected. Three COMT and 2 GCH1 tagging single-nucleotide polymorphisms (SNPs) were genotyped and analyzed for association with PPP-related activity impairment at 6 months after herniotomy. Fifty-five (12.8%) patients had moderate-to-severe pain-related activity impairment 6 months postoperatively as measured by Activity Assessment Scale (≥8.3). Patients with the G allele of COMT SNP rs6269 and C allele of COMT SNP rs4633 had less impairment (P = 0.03 and 0.01, respectively); in addition, the COMT haplotype GCG was associated with less impairment. For GCH1, the A allele of SNP rs3783641, T allele of rs8007267, and AT haplotype showed a protective effect trend (although nonsignificant; P = 0.08, 0.06, and 0.08, respectively). A prediction model of substantial PPP-related activity impairment, combining COMT and GCH1 SNPs with clinical, psychophysical, and psychological risk factors, had a "good" (0.8 < area under curve < 0.9) discriminatory power. These data suggest that functional variations in COMT and GCH1 combined with clinical factors are predictive of PPP-related impairment after groin herniotomy.
authors.affiliation: Departments of Anesthesiology and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA Yale Center for Analytical Sciences, Yale University, New Haven, CT, USA Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark Department of Surgery, Marienhospital Stuttgart, Stuttgart, Germany.
authors.forename: Inna
authors.initials: I
authors.lastname: Belfer
authors.forename: Feng
authors.initials: F
authors.lastname: Dai
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
authors.forename: Peter
authors.initials: P
authors.lastname: Finelli
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bittner
authors.forename: Eske K
authors.initials: EK
authors.lastname: Aasvang
mesh_terms: D000328:Adult; D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D006136:GTP Cyclohydrolase / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D059685:Herniorrhaphy / Q000009:adverse effects*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D006136:GTP Cyclohydrolase