Fan Q, Uring-Lambert B, Weill B, Gautreau C, Menkes C J, Delpech M
CNRS, ER 17-Institut Cochin de Génétique Moléculaire, Paris, France.
Eur J Immunogenet. 1993 Feb;20(1):11-21. doi: 10.1111/j.1744-313x.1993.tb00091.x.
Deficiency of complement component C4 is considered playing a role in the genetic predisposition for systemic lupus erythematosus (SLE). The purpose of this study was to characterize the genomic alterations of the C4 and CYP21 genes in 40 caucasoid patients with SLE by C4 allotyping and by RFLP analysis. Nineteen patients (47.5%) carried C4A null alleles and eight patients (20.0%) C4B null alleles. SLE patients had more frequent C4A null alleles (47.5%) than healthy individuals (20%) (chi 2 = 10.75; P < 0.005). The commonest molecular alteration in the patients with C4A null alleles was a large gene deletion affecting both C4A and CYP21A genes. However, among the patients with C4A null alleles, 16.7% persons had no detectable C4A deletion. The non-expression of C4A gene might be due to defects at various levels of gene expression (i.e. transcription and translation). Among the patients with C4B null alleles, 62.5% persons had no detectable gene lesion, whereas 37.5% showed a C4B deletion including both C4B/CYP21A or C4B/CYP21B genes. Duplication of the C4B gene was not rare in SLE patients, as we found 15.0% of the patients with a heterozygous C4B/CY21A gene duplication. The patients typed as having C4B gene homoduplication (B1,1) demonstrated two long C4B loci, whereas heteroduplication (B1,2) displayed two short loci, therefore the type of C4B gene duplication may be related to the gene length. In conclusion, C4 deficiencies observed in 26 of the 40 SLE patients studied were very heterogeneous. In every case, the gene alteration affected both C4 and CYP21 genes.
补体成分C4缺乏被认为在系统性红斑狼疮（SLE）的遗传易感性中起作用。本研究的目的是通过C4分型和限制性片段长度多态性（RFLP）分析来表征40例白种人SLE患者中C4和CYP21基因的基因组改变。19例患者（47.5%）携带C4A无效等位基因，8例患者（20.0%）携带C4B无效等位基因。SLE患者中C4A无效等位基因（47.5%）比健康个体（20%）更常见（χ² = 10.75；P < 0.005）。C4A无效等位基因患者中最常见的分子改变是影响C4A和CYP21A基因的大片段基因缺失。然而，在C4A无效等位基因患者中，16.7%的人未检测到C4A缺失。C4A基因不表达可能是由于基因表达的各个水平（即转录和翻译）存在缺陷。在C4B无效等位基因患者中，62.5%的人未检测到基因病变，而37.5%的人显示C4B缺失，包括C4B/CYP21A或C4B/CYP21B基因。C4B基因重复在SLE患者中并不罕见，因为我们发现15.0%的患者存在C4B/CY21A基因杂合重复。被分型为具有C4B基因纯合重复（B1,1）的患者表现出两个长的C4B基因座，而异合重复（B1,2）则表现出两个短的基因座，因此C4B基因重复的类型可能与基因长度有关。总之，在研究的40例SLE患者中有26例观察到的C4缺乏非常异质。在每种情况下，基因改变都影响C4和CYP21基因。
