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.
Perspective
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.
Key words: Pain genetics, temporomandibular joint disorders (TMD), association study, HTR2A, COMT, NR3C1, CAMK4, CHRM2, IFRD1, GRK5
Supported by NIH grants U01DE017018, DE016558, P01NS045685, R01DE016155, and F32DE019057, and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (DZ). The OPPERA program also acknowledges resources specifically provided for this project by the respective host universities: University at Buffalo, University of Florida, University of Maryland-Baltimore, and University of North Carolina-Chapel Hill.
Shad Smith, Roger Fillingim and Gary Slade are consultants and equity stock holders, and William Maixner and Luda Diatchenko are cofounders and equity stock holders in Algynomics, Inc., a company providing research services in personalized pain medication and diagnostics. Portions of these data were presented at the 2010 Annual Scientific Meeting of the American Pain Society in Baltimore, MD.
Supplementary data accompanying this article are available online at jpain.org and sciencedirect.com.
PII: S1526-5900(11)00738-3
doi:10.1016/j.jpain.2011.08.005
Published by Elsevier Inc.
