The Disablement Process in Rheumatoid Arthritis

类风湿关节炎的致残过程

基本信息

批准号：
7900518
负责人：
AGUSTIN ESCALANTE
金额：
$ 57万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7900518
关键词：
Address Affect American Candidate Disease Gene Cessation of life Characteristics Clinical Comorbidity Deformity Disease Disease Outcome Disease Pathway Environment Environmental Risk Factor Ethnic Origin Ethnic group Evaluation Event Foundations Funding Genes Genetic Genetic Variation Genotype Goals Grant Impairment Inflammation Intervention Joints Left Longevity Maps Measures Medical Mexican Americans Modeling Motion Names National Institute of Child Health and Human Development Not Hispanic or Latino Nucleotides Operative Surgical Procedures Outcome Pain Pathology Pathology processes Pathway interactions Patients Pattern Performance Pharmaceutical Preparations Phenotype Predisposition Principal Investigator Process Psychosocial Factor Publications Recruitment Activity Research Research Subjects Resources Rheumatoid Arthritis Right-On Risk Role Sample Size Severities Single Nucleotide Polymorphism Social Class Socioeconomic Status Staging Stratification Testing Variant Wood material biopsychosocial bone metabolism cartilage metabolism cigarette smoking cohort disability experience gene function joint injury member novel prevent psychosocial theories trait

项目摘要

DESCRIPTION (provided by applicant): Inflammation damages the joints of rheumatoid arthritis (RA) patients. They experience pain, loss of motion, physical disability and a shortened lifespan. Despite estimates suggesting Mexican Americans (MA) may be more susceptible to RA than other major U.S. ethnic groups, little is known about the clinical expression or outcome in RA in MA. Our goals are to identify optimal points for intervention to retard disablement in RA, and to understand the mechanisms of ethnic disparities. Toward these goals, we developed a novel biopsychosocial model of disability in RA, which guided our study of a multiethnic cohort of 779 RA patients. During the initial funding period from 1999 to 2005, we followed the cohort for 3,967 patient-years. Key findings from the initial period that we aim to study further include: First, a significant ethnic disparity in the clinical expression of RA, MA having more severe manifestations at every stage of the disablement process; and second, extreme variation among the patients in the accrual of joint damage. Our Specific Aims are: 1) To identify gene variants (single nucleotide polymorphisms, or SNPs), associated with the joint damage phenotype in RA, and to examine their downstream influence on the disablement process; 2) To examine the extent to which ethnic variation in the disablement process in RA is explained by genetic and environmental factors; and 3) To examine the influence of ethnicity, genetic and environmental factors on survival in RA. We will study MA and non-Hispanic White (NHW) members of the original RA cohort (n=655) and will recruit additional patients for a combined sample size of 500 MA and 500 NHW RA patients. We will follow patients longitudinally to evaluate the process of disablement, and survival. We will study 25 carefully selected candidate genes found previously to be associated with RA susceptibility and/or severity. In each gene, we will genotype an average of 20 SNPs, selected to capture the largest amount of regional genetic information, or for their potential to alter gene function. We will use Bayesian Quantitative Trait Nucleotide analysis (BQTN) to identify SNPs associated with joint damage. This research will advance current understanding of the genotype-phenotype relationship in RA, and of how genes and the environment contribute to ethnic disparities in the disablement process. SNPs associated with RA damage may be useful for risk stratification of patients, and may contribute to the discovery of novel targets for RA treatments.

描述（由申请人提供）：炎症会损害类风湿关节炎（RA）患者的关节。他们经历疼痛，运动丧失，身体残疾和寿命缩短。尽管估计表明墨西哥裔美国人（MA）可能比其他主要族裔更容易受到RA的影响，但对MA中RA中的临床表达或结果知之甚少。我们的目标是确定干预措施以阻碍RA的最佳点，并了解种族差异的机制。朝向这些目标，我们在RA中开发了一种新型的残疾生物心理社会模型，该模型指导了我们对779名RA患者的多民族队列的研究。在1999年至2005年的最初资助期间，我们跟随队列3,967例患者年。我们旨在进一步研究的最初时期的主要发现包括：首先，RA的临床表达中的重大种族差异，MA在残疾过程的每个阶段都具有更严重的表现；其次，患者的关节损害应计。我们的具体目的是：1）鉴定与RA中关节损伤表型相关的基因变异（单核苷酸多态性或SNP），并检查其下游对残疾过程的影响； 2）检查RA中残疾过程中种族变异的程度由遗传和环境因素解释； 3）检查种族，遗传和环境因素对RA生存的影响。我们将研究原始RA队列（n = 655）的MA和非西班牙裔白人（NHW）成员，并将招募500 MA和500 NHW RA患者的样本量的其他患者。我们将纵向关注患者，以评估残疾和生存过程。我们将研究25个以前发现与RA敏感性和/或严重程度有关的精心选择的候选基因。在每个基因中，我们的基因型平均为20个SNP，被选为捕获最大量的区域遗传信息或其改变基因功能的潜力。我们将使用贝叶斯定量性状核苷酸分析（BQTN）来识别与关节损伤相关的SNP。这项研究将提高对RA中基因型 - 表型关系的当前理解，以及基因和环境如何促进残疾过程中的种族差异。与RA损伤相关的SNP可能对患者的风险分层有用，并且可能有助于发现RA治疗的新靶标。