COMT and betaAR Polymorphism and Development of Painful TMD

产品说明：（申请人提供）疼痛性颞下颌关节紊乱病（TMD）是一种非常常见的口面疼痛病症，影响大部分人群，对女性有很强的偏好。发展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β 2-肾上腺素能受体（β 2-AR）（一种肾上腺素受体靶点）的特定遗传变异（单倍型）与人类疼痛感知和患肌源性TMD的风险相关。我们建议通过识别和功能表征编码COMT和β 2-AR的基因的完整单倍型结构来扩展我们对选定SNP的初步评估。我们将确定与疼痛感知、月经周期相关的躯体主诉以及发生肌源性TMD风险相关的单个单核苷酸多态性（SNP）和单倍型。为了实现这一目标，我们将对200名女性TMD患者和200名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，以研究COMT和β 2-AR基因多态性影响各自编码蛋白生物学功能的机制。通过阐明影响人类疼痛感知的遗传因素，这些研究将有助于我们了解肌源性TMD的病理生理学基础，并可能导致新的药物遗传学方法来诊断和治疗TMD患者。

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.