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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。结节病是一种病因不明的多系统肉芽肿性炎性疾病。结节病的遗传易感性是由家族聚集性和某些种族群体，特别是非洲裔美国人中较高的患病率报告提出的。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于16号染色体的着丝粒区域。我们没有发现在这一区域存在连锁的证据，可以排除引起结节病的相对危险度至少为5的显性基因或相对危险度至少为3的隐性基因。为寻找易感基因进行全基因组扫描的多中心研究已经完成，在基因组扫描中确定的六个候选区域的精细绘图也已完成。在入组的559对同胞对中，遗传分析显示，10.4%报告的全同胞对和1.4%报告的半同胞对的关系不正确，需要重新分类或从分析数据集中删除。最终的研究样本包括415个完整的和104个半同胞对完整的数据。这包括338个ASP。在兄弟姐妹对，感情状况与性别无关。利用Haseman-Elston回归分析，在1 p22、2 p25、5 p15 -13、5 q11、5 q35、9 q34、11 p15和20 q13上发现了P值小于0.05的连锁峰，其中最显著的连锁峰位于5 q11上（P=0.0005）。我们发现与先前报道的德国人口在染色体1 p和9 q的基因组扫描的连锁协议。基于在我们的研究人群中发现的多个连锁区域，很可能不止一个基因影响非裔美国人的结节病易感性。