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

项目总结（见说明）： AS和其他脊柱关节炎（SpA）相关疾病（如炎症性肠病（IBD）和银屑病）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和疾病特异性基因网络。在过去的几年中，轴性SpA已经作为一个独立的实体出现，已经制定了特定的标准。该提案旨在进一步评估AS患者一级亲属（FDR）的SpA谱，特别是新发轴性SpA，并评估 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例AS患者的炎性腰痛（IBP）和轴性SpA的FDR中对其进行了验证，这些将在其他FDR中进一步检查一系列其他SpA表现，以便具有更好的统计功效来计算每个分量的准确性（目标1）。我们将通过邮寄或通过临床研究单位（CPU）的临床/血清学评价向参与项目2的AS患者的所有FDR施用仪器，并将评估血清CRP以评估慢性炎症（来自亲自评估的那些）或从唾液样品中获得的DNA（来自通过邮寄检查的那些）（目标2）。已知与AS易感性相关的基因的遗传分析（HLA-B27，ERAP 1，IL 23 R，染色体2 p15和21 q22处的基因沙漠，等，比较受影响与未受影响的FDR（未受影响的FDR定义为年龄达到40岁，在问卷评估中没有任何SpA体征/症状）目的是在FDR中发现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岁以上个体的HLA-B27频率显著降低，我们将通过问卷调查或临床评价对FDR进行横断面评价，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。

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.