COMT & betaAR Polymorphism & Development of Painful TMD

COMT

• 批准号: 6896271
• 负责人: LUDA DIATCHENKO
• 金额: $ 36.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-05 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896271
• 关键词: beta adrenergic receptor; catechol methyltransferase; clinical research; female; genetic polymorphism; genetic susceptibility; human subject; menstrual cycle disorder; neurogenetics; pain threshold; patient oriented research; single nucleotide polymorphism; temporomandibular joint syndrome

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.

描述：（由申请人提供）疼痛的颞下颌疾病（TMD）是一种非常常见的口面疼痛状况，影响了大部分人口，对女性有很大的偏见。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，我们发现特定的遗传变异（单倍型），这些特定的儿茶酚胺-O-甲基转移酶（COMT），一种调节儿茶酚胺水平的酶以及Beta2-肾上腺素受体（beta2-ar）的酶（beta2-ar），AN与epinephrine的受体靶标相关，与人类疼痛相关联，并且与人类疼痛相关。我们建议通过识别和功能表征COMT和BETA2-AR代码的基因的完整单倍型结构来扩展对选定SNP的初步评估。我们将确定与疼痛感，与月经周期相关的躯体抱怨以及发展肌H的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的生化和分子生物学研究，这些研究将研究COMT和BETA2-AR基因中的多态性影响相应编码蛋白的生物学功能的机制。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对肌源性TMD潜在的病理生理学的理解，并可能导致新的药物遗传学方法来诊断和治疗TMD患者。