Genetic Variants Associated With Development of TMD and Its Intermediate Phenotypes: The Genetic Architecture of TMD in the OPPERA Prospective Cohort Study

JOURNAL OF PAIN

卷:14

Article

Smith, Shad B.^1,2  Mir, Ellen^1,3  Bair, Eric^1,2,3  Slade, Gary D.^1,4,5  Dubner, Ronald^7,8,9  Fillingim, Roger B.^10,11  Greenspan, Joel D.^7,8,9  Ohrbach, Richard¹²  Knott, Charles¹³  Weir, Bruce¹⁴  Maixner, William^1,2,6  Diatchenko, Luda^1,2,15,16,17 

[1] Univ N Carolina, Reg Ctr Neurosensory Disorders, Chapel Hill, NC USA

[2] Univ N Carolina, Dept Endodont, Chapel Hill, NC USA

[3] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[4] Univ N Carolina, Dept Dent Ecol, Chapel Hill, NC USA

[5] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[6] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA

[7] Univ Maryland, Sch Dent, Dept Oral & Maxillofacial Surg, Baltimore, MD 21201 USA

[8] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA

[9] Univ Maryland, Sch Dent, Brotman Facial Pain Ctr, Baltimore, MD 21201 USA

[10] Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, Gainesville, FL USA

[11] Pain Res & Intervent Ctr Excellence, Gainesville, FL USA

[12] SUNY Buffalo, Dept Oral Diagnost Sci, Buffalo, NY 14260 USA

[13] Battelle Mem Inst, Durham, NC USA

[14] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[15] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA

[16] McGill Univ, Dept Anesthesia, Montreal, PQ H3A 0G1, Canada

[17] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ H3A 0G1, Canada

关键词: Temporomandibular disorder;    genetic risk factors;    incidence;    chronic pain;    intermediate phenotypes;   

DOI  :  10.1016/j.jpain.2013.09.004

来源: Elsevier

【 摘 要 】

Genetic risk factors are believed to combine with environmental exposures and contribute to the risk of developing temporomandibular disorder (TMD). In this prospective cohort study, 2,737 people without TMD were assessed for common genetic variation in 358 genes known to contribute to nociceptive pathways, inflammation, and affective distress. During a median follow-up period of 2.8 years, 260 people developed first-onset TMD. Hazard ratios were computed as measures of association between 2,924 single-nucleotide polymorphisms and TMD incidence. After correction for multiple testing, no single single-nucleotide polymorphism was significantly associated with risk of onset TMD. However, several single-nucleotide polymorphisms exceeded Bonferroni correction for multiple comparison or false discovery rate thresholds (.05, .1, or .2) for association with intermediate phenotypes shown to be predictive of TMD onset. Nonspecific orofacial symptoms were associated with voltage-gated sodium channel, type I, alpha subunit (SCN1A, rs6432860, P = 2.77 x 10(-5)) and angiotensin l-converting enzyme 2 (ACE2, rs1514280, P = 4.86 x 10(-5)); global psychological symptoms with prostaglandin-endoperoxide synthase 1 (PTGS1, rs3842803, P = 2.79 x 10(-6)); stress and negative affectivity with amyloid-beta (A4) precursor protein (APP, rs466448, P = 4.29 x 10(-5)); and heat pain temporal summation with multiple PDZ domain protein (MPDZ, rs10809907, P = 3.05 x 10(-5)). The use of intermediate phenotypes for complex pain diseases revealed new genetic pathways influencing risk of TMD. (C) 2013 by the American Pain Society

【 授权许可】

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