A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families
A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families
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DOI：
10.1073/pnas.95.25.14875
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Behrens, TW
中科院分区：
文献类型：
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作者：
Gaffney, PM;Kearns, GM;Behrens, TW
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。先前的遗传学研究表明与 HLA II 类等位基因、补体基因缺陷和 Pc 受体多态性有关；然而，其他基因可能会影响 SLE 的易感性和发病机制。在这里，我们报告了 105 个 SLE 同胞对家族的全基因组微卫星标记筛选结果。通过使用多点非参数方法，在 HLA 基因座 (6p11-p21) [D6S257，对数对数 (lod) = 3.90，P = 0.000011] 附近和另外三个区域：16q13 (D16S415，lod = 3.64，P = 0.000022) 发现了最有力的连锁证据， 14q21-23（D14S276，lod = 2.81，P = 0.00016）和20p12（D20S186，lod = 2.62，P = 0.00025）。另外 9 个区域（1p36、1p13、1q42、2p15、2q21-33、3cent-q11、4q28、11p15 和 15q26）被确定为 Lod 分数大于或等于 1.00。这些数据支持这样的假设：多个基因（包括 HLA 区域的一个基因）影响人类 SLE 的易感性。
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 Pc 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 greater than or equal to 1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.