PMID- 25218601
OWN - NLM
STAT- MEDLINE
DCOM- 20150925
LR  - 20220408
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 155
IP  - 11
DP  - 2014 Nov
TI  - Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme 
      activity and pain.
PG  - 2390-9
LID - S0304-3959(14)00429-1 [pii]
LID - 10.1016/j.pain.2014.09.009 [doi]
AB  - Abnormalities in the enzymatic activity of catechol-O-methyltransferase (COMT) 
      contribute to chronic pain conditions, such as temporomandibular disorders (TMD). 
      Thus, we sought to determine the effects of polymorphisms in COMT and 
      functionally related pain genes in the COMT pathway (estrogen receptor 1 [ESR1], 
      guanosine-5-triphosphate cyclohydrolase 1 [GCH1], methylenetetrahydrofolate 
      reductase [MTHFR]) on COMT enzymatic activity, musculoskeletal pain, and 
      pain-related intermediate phenotypes among TMD cases and healthy control 
      subjects. Results show that the COMT rs4680 (val(158)met) polymorphism is most 
      strongly associated with outcome measures, such that individuals with the minor A 
      allele (met) exhibit reduced COMT activity, increased TMD risk, and increased 
      musculoskeletal pain. Epistatic interactions were observed between the COMT 
      rs4680 polymorphism and polymorphisms in GCH1 and ESR1. Among individuals with 
      the COMT met allele, those with 2 copies of the GCH1 rs10483639 minor G allele 
      exhibit normalized COMT activity and increased mechanical pain thresholds. Among 
      individuals with the COMT val allele, those with 2 copies of the ESR1 rs3020377 
      minor A allele exhibit reduced COMT activity, increased bodily pain, and poorer 
      self-reported health. These data reveal that the GCH1 minor G allele confers a 
      protective advantage among met carriers, whereas the ESR1 minor A allele is 
      disadvantageous among val carriers. Furthermore, these data suggest that the 
      ability to predict the downstream effects of genetic variation on COMT activity 
      is critically important to understanding the molecular basis of chronic pain 
      conditions.
CI  - Copyright (c) 2014 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Smith, Shad B
AU  - Smith SB
AD  - Center for Pain Research and Innovation, School of Dentistry, University of North 
      Carolina, Chapel Hill, NC, USA.
FAU - Reenila, Ilkka
AU  - Reenila I
AD  - Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, 
      Finland.
FAU - Mannisto, Pekka T
AU  - Mannisto PT
AD  - Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, 
      Finland.
FAU - Slade, Gary D
AU  - Slade GD
AD  - Center for Pain Research and Innovation, School of Dentistry, University of North 
      Carolina, Chapel Hill, NC, USA.
FAU - Maixner, William
AU  - Maixner W
AD  - Center for Pain Research and Innovation, School of Dentistry, University of North 
      Carolina, Chapel Hill, NC, USA.
FAU - Diatchenko, Luda
AU  - Diatchenko L
AD  - Center for Pain Research and Innovation, School of Dentistry, University of North 
      Carolina, Chapel Hill, NC, USA; Alan Edwards Pain Centre For Research on Pain, 
      McGill University, Montreal, Canada.
FAU - Nackley, Andrea G
AU  - Nackley AG
AD  - Center for Pain Research and Innovation, School of Dentistry, University of North 
      Carolina, Chapel Hill, NC, USA. Electronic address: 
      andrea_nackley@dentistry.unc.edu.
LA  - eng
GR  - K12 HD052191/HD/NICHD NIH HHS/United States
GR  - L30 NS075905/NS/NINDS NIH HHS/United States
GR  - P01 NS045685/NS/NINDS NIH HHS/United States
GR  - R01 NS072205/NS/NINDS NIH HHS/United States
GR  - L30 DE017059/DE/NIDCR NIH HHS/United States
GR  - K12 DE022793/DE/NIDCR NIH HHS/United States
GR  - U01 DE017018/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140916
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - EC 2.1.1.6 (COMT protein, human)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Case-Control Studies
MH  - Catechol O-Methyltransferase/*genetics/metabolism
MH  - Epistasis, Genetic/*genetics
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - GTP Cyclohydrolase/*genetics/metabolism
MH  - Genotype
MH  - Humans
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
MH  - Middle Aged
MH  - Mood Disorders/etiology
MH  - Pain/*enzymology/*genetics/psychology
MH  - Pain Perception
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC4253645
MID - NIHMS635047
OTO - NOTNLM
OT  - Catecholamines
OT  - Fibromyalgia
OT  - Gene expression
OT  - Gene-gene interaction
OT  - Temporomandibular disorders
EDAT- 2014/09/15 06:00
MHDA- 2015/09/26 06:00
PMCR- 2015/11/01
CRDT- 2014/09/15 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/07/29 00:00 [revised]
PHST- 2014/09/04 00:00 [accepted]
PHST- 2014/09/15 06:00 [entrez]
PHST- 2014/09/15 06:00 [pubmed]
PHST- 2015/09/26 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - S0304-3959(14)00429-1 [pii]
AID - 10.1016/j.pain.2014.09.009 [doi]
PST - ppublish
SO  - Pain. 2014 Nov;155(11):2390-9. doi: 10.1016/j.pain.2014.09.009. Epub 2014 Sep 16.