Axial Spondyloarthritis (SpA)and HLA-B27 in First Degree Relatives of AS Patient

AS 患者一级亲属中的中轴型脊柱关节炎 (SpA) 和 HLA-B27

• 批准号: 8546232
• 负责人: JOHN Duffin REVEILLE
• 金额: $ 6.35万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8546232
• 关键词: 2p15; Acute; Adult; Affect; Age; Americas; Ankylosing spondylitis; Anterior uveitis; Arthritis; Back Pain; Biological Markers; Blood; Cardiovascular Diseases; Chromosomes; Chronic; Clinical; Clinical Research; Collaborations; Comorbidity; DNA; Data; Diabetes Mellitus; Disease; Disease susceptibility; Evaluation; Family member; First Degree Relative; Frequencies; Funding; Genes; Genetic; Genetic Markers; HLA-B27 Antigen; Health; Hypertension; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Instruction; Junk DNA; Longevity; Low Back Pain; Mails; Major Histocompatibility Complex Gene; Malignant Neoplasms; Manuscripts; National Health and Nutrition Examination Survey; Pathogenesis; Patients; Peripheral; Persons; Phenotype; Predisposition; Prevalence; Program Research Project Grants; Psoriasis; Psoriatic Arthritis; Questionnaires; Reactive Arthritis; Saliva; Sampling; Serological; Serum; Signs and Symptoms; Specificity; Spondylarthritis; Spondylitis; Undifferentiated; Variant; Visceral; base; disease phenotype; genetic analysis; genome wide association study; hypercholesterolemia; instrument; proband; research clinical testing; screening

PROJECT SUMMARY (See instructions): Recent findings from genomewide association studies in AS and other spondyloarthritis (SpA)-related diseases, such as inflammatory bowel disease (IBD) and psoriasis suggest networks of shared and disease specific genes in pathogenesis. In the past few years, axial SpA has emerged as a discrete entity for which specific criteria have been developed This proposal is aimed at further evaluation the spectrum of SpA in first degree relatives (FDRs) of AS patients, particularly of new onset axial SpA, and to assess co-morbidities that could explain the diminishing frequency of HLA-B27 with age. Having developed an instrument through the U.S. National Health and Nutrition Examination Survey (NHANES), and validated it in over 137 FDRs of AS patients for inflammatory low back pain (IBP) and axial SpA, which will be further examined in additional FDRs with the range of other SpA manifestations in order to have a better statistical power for calculation of accuracy of each component (Aim 1). We will administer the instrument to all FDR's of AS patients participating in Project 2 either by mail or by clinical/ serologic evaluation in the Clinical Research Units (CPU's) and serum CRP will be assessed to assess chronic inflammation (from those evaluated in person) or DNA obtained from saliva samples (from those examined by mail) (Aim 2). Genetic analysis of genes known to be associated with AS susceptibility (HLA-B27, ERAPl, IL23R, gene deserts at chromosome 2p15 and 21q22, etc will be carried out comparing affected versus unaffected FDR's (an unaffected FDR defined at having reached the age of 40 years without any signs/symptoms of SpA on questionaire evaluation) with the intent of finding potential biomarkers of disease susceptibility in the FDRs. Based on data from the 2009 NHANES study showing a significantly diminished frequency of HLA-B27 in individuals over the age of 50 years, we will carry out a cross-sectional evaluation in FDRs, by questionnaire or clinical evaluation, for comorbidities potentially associated with SpA, particularly cardiovascular disease (Aim 3) and also hyperiipidemia/ hypercholesterolemia, hypertension, diabetes mellitus, and malignancy.

项目摘要（参见说明）： AS 和其他脊柱关节炎 (SpA) 相关疾病（例如炎症性肠病 (IBD) 和牛皮癣）的全基因组关联研究的最新发现表明，发病机制中存在共享基因和疾病特异性基因网络。在过去的几年中，中轴型 SpA 已成为一个独立的实体，并为其制定了具体标准。该提案旨在进一步评估 AS 患者一级亲属 (FDR) 中的 SpA 谱系，特别是新发中轴型 SpA，并评估合并症 可以解释 HLA-B27 的频率随着年龄的增长而减少。通过美国国家健康和营养检查调查 (NHANES) 开发了一种仪器，并在超过 137 个 AS 患者炎症性腰痛 (IBP) 和中轴型 SpA 的 FDR 中对其进行了验证，并将在其他 FDR 中进一步检查其范围的其他 SpA 表现，以便有更好的统计能力来计算每个组件的准确性（目标 1）。我们将为所有 FDR 的 AS 患者使用该仪器 通过邮寄或在临床研究单位 (CPU) 进行临床/血清学评估参与项目 2，将评估血清 CRP，以评估慢性炎症（来自亲自评估的样本）或从唾液样本中获得的 DNA（来自通过邮寄检查的样本） ）（目标 2）。已知与 AS 易感性相关的基因的遗传分析（HLA-B27、ERAP1、IL23R、染色体 2p15 上的基因荒漠） 和 21q22 等，将比较受影响与未受影响的 FDR（未受影响的 FDR 定义为在问卷评估中年满 40 岁且没有任何 SpA 体征/症状），目的是在 FDR 中寻找疾病易感性的潜在生物标志物。基于 2009 年 NHANES 研究的数据显示，50 岁以上个体中 HLA-B27 的频率显着降低 几年后，我们将通过问卷调查或临床评估，对 FDR 进行横断面评估，以了解可能与 SpA 相关的合并症，特别是心血管疾病（目标 3）以及高脂血症/高胆固醇血症、高血压、糖尿病和恶性肿瘤。