OK COBRE: GENETIC ASSOCIATION IN PEDIATRIC SLE PATIENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，具有多种临床表现，可影响所有种族、性别和年龄组。大约10%的SLE患者在18岁之前被诊断出来。儿童期发病的SLE往往更为严重，其临床病程也更具侵袭性。尽管已经进行了大量研究，描述SLE的遗传学特征，但没有一个研究集中在儿科发病亚组上。我们假设，儿科发病队列将丰富遗传效应，并且在该人群中发现的遗传风险因素也将赋予成人发病SLE患者风险。我们之前收集了三组小儿SLE患者和匹配的对照组，包括临床数据、血清样本和DNA。我们计划使用Affymetrix基因芯片简化我们对儿科发病SLE患者易感基因的搜索，该芯片允许同时在500,000个位点进行基因分型。一旦第一阶段的基因分型完成，结果将与数据库进行比较，并确定第二阶段SNP分型的优先顺序。前500种效果将在第二组儿科发病SLE病例和对照组中进行表征。预计这些效应中只有一小部分将得到证实，但那些可以复制的效应可能代表真正的SLE易感位点，无论是在成人还是儿童中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that presents with a variety of clinical manifestations and affects all races, genders, and age groups. About 10% of SLE patients are diagnosed by age 18. SLE that has onset in childhood tends to be more severe and to have a more aggressive clinical course. Although numerous studies have been performed characterizing the genetics of SLE, none of them have focused on the pediatric-onset subgroup. We hypothesize that pediatric-onset cohorts will be enriched for genetic effects, and that the genetic risk factors found in this population will also confer risk in adult-onset SLE patients. We have previously collected three cohorts of pediatric SLE patients and matched controls, including clinical data, serum samples, and DNA. We plan to streamline our search for susceptibility genes in pediatric-onset SLE patients using the Affymetrix GeneChip, which allows simultaneous genotyping at 500,000 loci. Once the first phase of genotyping is complete, results will be compared with the database and priorities for the second phase of SNP typing will be established. The top 500 effects will be characterized in the second cohort of pediatric-onset SLE cases and controls. It is expected that only a subset of these effects will be confirmed, but those effects that can be replicated are likely to represent true SLE susceptibility loci, both in adults and children.