Gaffney P M, Kearns G M, Shark K B, Ortmann W A, Selby S A, Malmgren M L, Rohlf K E, Ockenden T C, Messner R P, King R A, Rich S S, Behrens T W
University of Minnesota Medical School, 312 Church Street SE, Minneapolis, MN 55455, USA.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14875-9. doi: 10.1073/pnas.95.25.14875.
Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disease characterized by the production of pathogenic autoantibodies. Previous genetic studies have suggested associations with HLA Class II alleles, complement gene deficiencies, and Fc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesis. Here, we report the results of a genome-wide microsatellite marker screen in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) [D6S257, logarithm of odds (lod) = 3.90, P = 0.000011] and at three additional regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21-23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Another nine regions (1p36, 1p13, 1q42, 2p15, 2q21-33, 3cent-q11, 4q28, 11p15, and 15q26) were identified with lod scores >/=1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.
系统性红斑狼疮（SLE）是一种自身免疫性多系统炎症性疾病，其特征是产生致病性自身抗体。先前的基因研究表明，它与人类白细胞抗原（HLA）II类等位基因、补体基因缺陷和Fc受体多态性有关；然而，很可能还有其他基因导致SLE易感性和发病机制。在此，我们报告了对105个SLE同胞对家庭进行全基因组微卫星标记筛查的结果。通过使用多点非参数方法，在HLA基因座（6p11 - p21）附近发现了最强的连锁证据[D6S257，优势对数（lod）= 3.90，P = 0.000011]，以及另外三个区域：16q13（D16S415，lod = 3.64，P = 0.000022）、14q21 - 23（D14S276，lod = 2.81，P = 0.00016）和20p12（D20S186，lod = 2.62，P = 0.00025）。另外九个区域（1p36、1p13、1q42、2p15、2q21 - 33、3cent - q11、4q28、11p15和15q26）的lod得分≥1.00。这些数据支持了多个基因（包括HLA区域中的一个基因）影响人类SLE易感性的假设。
