COMT and betaAR Polymorphism and Development of Painful TMD

COMT和betaAR多态性与痛苦TMD的发展

• 批准号: 7365142
• 负责人: LUDA DIATCHENKO
• 金额: $ 33.11万
• 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/7365142
• 关键词: AR gene; Adrenergic Receptor; Affect; Alleles; Biochemical; Biological; Biological Process; Blood Cells; Blood specimen; Case-Control Studies; Catabolism; Cataloging; Catalogs; Catecholamines; Clinical Data; Code; Cohort Studies; Condition; Cultured Cells; DNA; Data; Data Set; Development; Diagnosis; Dopamine; Enzymes; Epinephrine; Female; Frequencies; Functional disorder; Gene Structure; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genotype; Haplotypes; Heating; Human; In Vitro; Individual; Lead; Link; Measures; Mechanics; Menstrual cycle; Metabolism; Methyltransferase; Methyltransferase Gene; Molecular; Neuraxis; Norepinephrine; Nucleotides; Numbers; Opioid Receptor Binding; Orofacial Pain; Pain; Pain-Free; Participant; Patients; Perception; Pharmacogenetics; Phenotype; Population; Property; Prospective Studies; Proteins; Receptor Gene; Recruitment Activity; Regulation; Relative (related person); Research; Research Personnel; Risk; Risk Factors; Series; Severity of illness; Signs and Symptoms; Single Nucleotide Polymorphism; Stimulus; Sum; Temporomandibular Joint Disorders; Transcript; Translations; Variant; base; case control; cohort; disorder control; genetic risk factor; genetic variant; human female; novel; programs; prospective; receptor; receptor density

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）疼痛性颞下颌紊乱（TMD）是一种非常常见的口腔面部疼痛疾病，影响了很大一部分人群，其中以女性为主。发生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）与人类疼痛感知和发生肌源性TMD的风险相关。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snp的初步评估。我们将确定个体单核苷酸多态性（snp）和单倍型，它们与痛觉、月经周期相关的躯体不适以及发生肌源性TMD的风险相关。为此，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，以检验COMT和Beta2-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，并可能为TMD患者的诊断和治疗提供新的药物遗传学方法。