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

项目总结(见说明)： 最近对AS和其他脊椎关节炎(SpA)相关疾病，如炎症性肠病(IBD)和牛皮癣的全基因组相关性研究的最新发现表明，共同的和疾病特异的基因网络在发病机制中存在。在过去的几年里，轴性SpA已经成为一个独立的实体，已经为其制定了特定的标准。这项建议旨在进一步评估AS患者的一级亲属(FDR)的SpA谱，特别是新发的中轴性SpA，并评估 可以解释人类白细胞抗原B27基因频率随年龄增长而递减的原因。通过美国国家健康和营养检查调查(NHANES)开发了一种工具，并在137多名AS患者的FDR中进行了验证，这些患者患有炎症性下腰痛(IBP)和轴性SpA，将进一步在其他FDR中与其他SpA表现一起进行检查，以便有更好的统计能力来计算每个组成部分的准确性(目标1)。我们将通过邮寄或通过临床研究单位的临床/血清学评估将该仪器应用于参与项目2的AS患者的所有FDR，并将评估血清CRP以评估慢性炎症(来自亲自评估的人)或从唾液样本(来自邮寄检查的人)获得的DNA(目标2)。将对已知与AS易感性相关的基因(人类白细胞抗原B27、ERAP1、IL23R、染色体2p15和21q22上的基因缺失等)进行遗传分析，比较受影响和未受影响的FDR(未受影响的FDR定义为已年满40岁，在问卷调查中没有任何SpA迹象/症状)，目的是在FDR中寻找潜在的疾病易感性生物标记物。根据2009年NHANES研究的数据显示，50岁以上的人群中，人类白细胞抗原B27的频率显著降低，我们将通过问卷调查或临床评估，在FDR中进行一项横断面评估，以确定可能与SpA相关的并发症，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.