GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

由NIAMS RFA(AR-93-006)提供的关于妇女和少数族裔狼疮的资金使收集系统性红斑狼疮多基因的非裔美国人家系和进行基因组扫描成为可能。在最初的31个家系中，我们发现了至少7个与非裔美国人狼疮相关的潜在联系。其中，FcGammaRIIA基因座为连锁提供了最一致的证据，LOD得分为3.37%，并进行了可能显著影响的同胞对分析(p=0.0005)。受影响的同胞对为周围五个大约35 cM的基因座的连锁提供了广泛的支持。D1s3462也有Lod=3.50连锁的提示证据。D3s1053和D17s2180两种等位基因共享算法获得的LOD大于1.5(D11s2002、D11s1392和D3s1766)或P<0.01的基因座有5个，其效应主要存在于非裔美国人家系中。另外三个基因座似乎对起源于非洲和欧洲(LOD=2至2.5)的狼疮多基因家系有影响。我们正在重新提交这项提案，以便获得继续这项工作所需的资源。我们在接下来的资助期间的具体目标是：1.扩大狼疮的非裔美国人家系的多样性；2.令人信服地建立连锁并寻找FcGammaRIIA和D1s3462附近的致病基因；3.确定非裔美国人家系中与狼疮存在其他连锁关系；4.通过检查它们与已建立的连锁的关系来评估其他表型定义；5.探索狼疮和抗核抗体效价作为这些家系中数量性状表型的标准。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.