Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus
Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus
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DOI：
10.1172/jci119217
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发表时间：
1997-02-15
影响因子：
15.9
通讯作者：
Notter, JI
中科院分区：
文献类型：
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作者：
Tsao, BP;Cantor, RM;Notter, JI
遗传易感性赋予系统性红斑狼疮（SLE）的重大风险。MHC区域和其他多态性位点与SLE相关。因为更令人信服的证据参与的遗传位点包括连锁，我们测试了一个候选区域同源的小鼠SLE易感区域在52 SLE影响同胞来自三个种族。我们分析了来自人类染色体1 q31-q42区域的7个微卫星标记，该区域对应于小鼠1号染色体的端粒末端，该区域是小鼠狼疮的具体表现，包括肾小球肾炎和IgG抗染色质，已被映射。将这7个标记中的每一个在受影响的同胞对中的平均等位基因共享与它们的期望值0.50进行比较，只有位于1 q41-q42的5个标记显示出连锁的证据（P = 0.0005-0.08）。IgG抗染色质的血清水平也显示了与这五种标记物中的两种（P = 0.04）相关联的证据，表明这种表型在小鼠和人类之间是保守的。与预期的随机分布相比，三个民族患病同胞的单倍型共享率有增加的趋势（P < 0.01）。我们的结论是，这个候选1 q41-q42区域可能包含一个易感基因，在多个种族群体中赋予SLE的风险。
Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.