GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

NIAMS RFA （AR-93-006）对女性和少数民族狼疮的资助使得收集具有多重系统性红斑狼疮的非裔美国人血统和进行基因组扫描成为可能。在前31个谱系中，我们发现了至少7个潜在的联系，这些联系对于非裔美国人的狼疮来说是相对特定的。其中，FcgammaRIIA基因座提供了最一致的证据，其lod评分为3.37，可能显著影响兄弟姐妹对分析（p=0.0005）。受影响的兄弟姐妹对提供了来自5个周围基因座的广泛支持，跨度约为35 cM。d13s3462在lod=3.50时也有关联的暗示性证据。另外五个基因座通过两种应用的等位基因共享算法（D3s1053和D17s2180）获得的load值大于1.5 （D11s2002， D11s1392和D3s1766）或p值小于0.01，并且主要在非裔美国人家系中产生影响。另外三个位点似乎对非洲和欧洲血统的多重家族狼疮都有影响（lod=2至2.5）。我们重新提出这项建议是为了获得继续这项工作所需的资源。我们在即将到来的资助期的具体目标是：1。为了扩大非裔美国人狼疮谱系的收藏，2。为了令人信服地建立联系并追求FcgammaRIIA和d13s3462,3附近负责基因的身份。为了在非洲裔美国人的血统中建立与狼疮的其他联系，通过检查其与已建立的联系的关系来评估其他表型定义；目的探讨狼疮的诊断标准及作为数量性状表型的抗核抗体滴度。这项研究的结果可能有助于了解非裔美国人系统性红斑狼疮的遗传学。

Funding from NIAMS RFA (AR-93-006) on Lupus in Women and Minorities made possible the collection of African-American pedigrees who were multiplex for systemic lupus erythematosus and the performance of a genome scan. In the first 31 pedigrees, we have found at least seven potential linkages which are relatively specific for lupus in African-Americans. Of these, the FcgammaRIIA locus provides the most consistent evidence for linkage with a lod score of 3.37 and a possibly significant affected sib-pair analysis (p=0.0005). The affected sib-pairs provide broad support for linkage from five of the surrounding loci spanning approximately 35 cM. D1s3462 also has suggestive evidence for linkage at lod=3.50. Five other loci obtain lod greater than 1.5 (D11s2002, D11s1392 and D3s1766) or p less than 0.01 by two applied allele sharing algorithms (D3s1053 and D17s2180) and have an effect which is predominately in the African-American pedigrees. Three additional loci appear to have effects found in families multiplex for lupus of both African and European origin (lod=2 to 2.5). We are resubmitting this proposal in order to obtain the resources with which to continue this work. Our specific aims for the coming funding period are: 1. To enlarge the collection of African-American pedigrees multiplex for lupus, 2. To convincingly establish linkage and pursue the identity of the genes responsible near FcgammaRIIA and D1s3462, 3. To establish the presence of other linkages with lupus in African-American pedigrees, 4. To evaluate other phenotype definitions by examining their relationship with the linkages established, and 5. To explore the criteria for lupus and the antinuclear antibody titer as quantitative trait phenotypes in these families. Results from this study are likely to contribute to understanding the genetics of systemic lupus erythematosus in African-Americans.