GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

非裔美国人结节病的遗传流行病学

• 批准号: 7420622
• 负责人: MICHAEL C IANNUZZI
• 金额: $ 0.74万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420622
• 关键词: chromosomes; epidemiology; genes; genetics; genome; sarcoidosis

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. Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk at least 5, or a recessive gene with relative risk at least 3, causing sarcoidosis. A multicenter study to perform a whole genome scan in the search for susceptibility genes has been completed, as has fine mapping of six candidate regions identified in the genome scan. In the total 559 sib pairs that were enrolled, genetic analyses revealed incorrectly specified relationships that required reclassification or removal from the analysis dataset of 10.4% of reported full and 1.4% of reported half sib pairs. The final study sample comprised 415 full and 104 half sib pairs with complete data. This inclused 338 ASPs. Within sib pairs, affection status was not associated with sex. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak t D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。结节病是一种病因不明的多系统肉芽肿性炎症性疾病。关于家族聚集性和某些种族群体，特别是非裔美国人的高患病率的报道表明，遗传性结节病易感性。肉芽肿性炎症性疾病Blau综合征和克罗恩病的候选基因已经定位在16号染色体的着丝粒区域。我们在这个一般区域没有发现连锁的证据，并可能从中排除相对风险至少为5的显性基因或相对风险至少为3的隐性基因，从而导致结节病。一项进行全基因组扫描以寻找易感基因的多中心研究已经完成，基因组扫描中确定的六个候选区域的精细图谱也已经完成。在总共登记的559对同胞中，遗传分析揭示了不正确指定的关系，需要重新分类或从分析数据集中删除10.4%的报告的全同胞对和1.4%的报告的半同胞对。最终的研究样本包括415对全同胞和104对半同胞，数据完整。其中包括338个ASP。在兄弟姐妹中，情感状况与性别无关。经Haseman-Elston回归分析，在染色体1p22、2p25、5p15-13、5q11、5q35、9q34、11p15和20q13上出现了P值小于0.05的连锁峰，其中以5q11上的tD5S2500最为显著(P=0.0005)。我们发现与先前报道的位于染色体1p和9q的德国人群的基因组扫描结果相一致。根据我们研究人群中发现的多个连锁提示区域，很可能有不止一个基因影响非裔美国人的结节病易感性。