Genome scan of human systemic lupus erythematosus:: Evidence for linkage on chromosome 1q in African-American pedigrees
Genome scan of human systemic lupus erythematosus:: Evidence for linkage on chromosome 1q in African-American pedigrees
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DOI：
10.1073/pnas.95.25.14869
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Harley, JB
中科院分区：
文献类型：
--
作者：
Moser, KL;Neas, BR;Harley, JB
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征在于产生针对细胞内抗原的自身抗体，所述细胞内抗原包括DNA、核糖体P、Ro（SS-A）、La（SS-B）和剪接体。病因学怀疑涉及遗传和环境因素。遗传参与的证据包括：与HLA-DR 3、HLA-DR 2、Fc γ受体（Fc γ R）IIA和IIIA、遗传性补体成分缺陷、家族聚集、单卵双生子一致性> 20%、λ（s）> 10、1 q41 -42的假定连锁和一致发展狼疮的近交系小鼠品系的关联。我们已经完成了94个扩展的多重家系的基因组扫描，使用基于模型的连锁分析。在非裔美国人的染色体1 q41、1 q23和11 q14 -23;在欧裔美国人的染色体14 q11、4p 15、11 q25、2 q32、19 q13、6 q26 -27和12 p12 -11; 1 q23、13 q32、20 q13和1 q31。Fc γ RIIA候选多态性在1 q23（在非裔美国人中lod = 3.37）的效应与狼疮鼠模型中的连锁同线。同胞对和多点非参数分析也支持用两点lod得分分析（lod > 2.0）检测到的9个位点的连锁（P < 0.05）。我们的研究结果与SLE遗传易感性的假设复杂性一致，并说明种族起源可能影响这些遗传效应的特定性质。
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fc gamma receptors (Fc gamma R) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambda(s) > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log(10) of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the Fc gamma RIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.