title: Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study.
abstract: Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1,442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3,295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously reported associations between TMD and 2 genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD, and they identify potential targets for therapeutic intervention.
  
  
  CONCLUSIONS
  Genetic risk factors for TMD pain were explored in the case-control component of the OPPERA cooperative agreement, a large population-based prospective cohort study. Over 350 candidate pain genes were assessed using a candidate gene panel, with several genes displaying preliminary evidence for association with TMD status.
authors.affiliation: Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, North Carolina 27514, USA.
authors.forename: Shad B
authors.initials: SB
authors.lastname: Smith
authors.forename: Dylan W
authors.initials: DW
authors.lastname: Maixner
authors.forename: Joel D
authors.initials: JD
authors.lastname: Greenspan
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Roger B
authors.initials: RB
authors.lastname: Fillingim
authors.forename: Richard
authors.initials: R
authors.lastname: Ohrbach
authors.forename: Charles
authors.initials: C
authors.lastname: Knott
authors.forename: Gary D
authors.initials: GD
authors.lastname: Slade
authors.forename: Eric
authors.initials: E
authors.lastname: Bair
authors.forename: Dustin G
authors.initials: DG
authors.lastname: Gibson
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Zaykin
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Weir
authors.forename: William
authors.initials: W
authors.lastname: Maixner
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D059350:Chronic Pain / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D013705:Temporomandibular Joint Disorders / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
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