GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

NIAMS RFA（AR-93-006）对妇女和少数民族狼疮的资助使得收集系统性红斑狼疮多发的非洲裔美国人谱系和进行基因组扫描成为可能。 在前31个家系中，我们发现了至少7个潜在的联系，这些联系对非裔美国人的狼疮相对特异。 其中，Fc γ RIIA基因座提供了最一致的连锁证据，lod评分为3.37，可能显著影响同胞对分析（p=0.0005）。 受影响的同胞对为来自周围五个基因座（跨度约35 cM）的连锁提供了广泛的支持。 D1 s3462在lod=3.50时也有连锁的暗示性证据。 通过两种应用的等位基因共享算法（D3 s1053和D17 s2180），其他五个基因座获得的lod大于1.5（D11 s2002、D11 s1392和D3 s1766）或p小于0.01，并且具有在非裔美国人谱系中占主导地位的影响。 三个额外的基因座似乎有影响，发现在家庭多重狼疮的非洲和欧洲的起源（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。 我们在下一个资助期内的具体目标是：1.为了扩大收集非洲裔美国人谱系多发性狼疮，2。为了令人信服地建立联系，并追求附近的Fc γ RIIA和D1 s3462，3，负责基因的身份。为了建立与非裔美国人家系中狼疮的其他联系，4。通过检查它们与所建立的连锁的关系来评估其他表型定义，以及5.探讨该家系狼疮的诊断标准及抗核抗体滴度作为数量性状表型的意义。 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.