COMT and betaAR Polymorphism and Development of Painful TMD

描述：(由申请人提供)痛性颞下颌关节紊乱病(TMD)是一种非常常见的口腔面部疼痛状况，影响很大比例的人类人口，对女性有强烈的偏见。患TMD的风险和疾病的严重程度与对疼痛的普遍敏感性有关。在初步研究中，我们发现编码儿茶酚胺-O-甲基转移酶(COMT)(一种调节儿茶酚胺水平的酶)和β2-肾上腺素能受体(β2-AR)的特定遗传变异(单倍型)与人类的痛觉和发生肌源性TMD的风险有关。我们建议通过鉴定和功能表征编码COMT和Beta2-AR的基因的完整单倍型结构来扩展我们对选定的SNPs的初步评估。我们将确定与痛觉、月经周期相关的躯体症状以及发生肌源性TMD风险相关的个体单核苷酸多态(SNPs)和单倍型。为此，我们将对200例女性TMD患者和200例女性对照患者进行病例对照研究。我们还将进行一系列生化和分子生物学研究，以检验COMT和Beta2-AR基因的多态如何影响各自编码蛋白质的生物学功能。通过阐明影响人类痛觉的遗传因素，这些研究将有助于我们理解肌源性TMD的病理生理学基础，并可能为TMD患者的诊断和治疗带来新的药物遗传学方法。

DESCRIPTION: (provided by the applicant) Painful temporomandibular disorder (TMD) is a very common orofacial pain condition that affects a large proportion of the human population with a strong bias towards females. The risk of developing TMD and the severity of the disease are associated with a generalized sensitivity to pain. In preliminary studies, we found that specific genetic variants (haplotypes) that code for catecholamine-O-methyltransferase (COMT), an enzyme regulating catecholamine levels, and Beta2-adrenergic receptor (Beta2-AR), a receptor target for epinephrine, are associated with human pain perception and the risk of developing a myogenous TMD. We propose to extend our preliminary assessments of selected SNPs by identifying and functionally characterizing the full haplotype structure of the genes that code for COMT and Beta2-AR. We will identify individual single nucleotide polymorphisms (SNPs) and haplotypes that are associated with pain perception, menstrual cycle related somatic complaints, and the risk of developing myogenous TMD. In order to accomplish this, we will conduct a case-control study on 200 female TMD patients and 200 female control patients. We will also conduct a series of biochemical and molecular biological studies that will examine the mechanisms by which polymorphisms in COMT and Beta2-AR genes affect the biological functions of the respective coded proteins. By elucidating the genetic factors that influence human pain perception, these studies will contribute to our understanding of the pathophysiology underlying myogenous TMD and may lead to new pharmacogenetic approaches to the diagnosis and treatment of TMD patients.