Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity
Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity
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DOI：
10.1007/s002510050561
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发表时间：
1999-09-01
期刊：
影响因子：
3.2
通讯作者：
Perl, A
中科院分区：
文献类型：
--
作者：
Magistrelli, C;Samoilova, E;Perl, A
抗核自身抗体是系统性红斑狼疮（SLE）的标志。HRES-1/p28（一种28000 M-r核蛋白）的自身抗体常见于SLE患者。HRES-1是一种单拷贝内源性逆转录病毒元件，定位于人类1号染色体q42。一个多态的Hin dIII位点定义了基因组位点的两种不同的等位基因形式，HRES-1/1探针[5.5千碱基（kb）]对三个多态片段进行了检测，可以区分三种基因型：I，只有5.5 kb片段；II，仅3.7 kb和1.8 kb片段；从ⅰ型和ⅱ型纯合的人DNA样本中克隆HRES-1基因座，鉴定出HRES-1多态位点为长末端重复区653位的G - C过渡位点。家族研究显示HRES-1位点的Hin dIII基因型以孟德尔模式遗传，SLE患者中基因I型相对于基因III型的相对频率（14:40=0.35）比100个种族匹配的对照供者（47:43 = 1.09;P = 0.0084）低3.1倍（14:40=0.35）。SLE患者基因I型和基因II型等位基因的频率（68/ 52）低于正常供者（137/63；P=0.033），提示HRES-1基因座的基因I型等位基因可能对SLE具有保护作用。重组HRES-1/p28在基因I型患者中有4/14（29%）和13/19（68%）具有Western blot血清反应性（P < 0.05）
Antinuclear autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Autoantibodies to HRES-1/p28, a 28 000 M-r nuclear protein, commonly occur in patients with SLE. HRES-1 is a single-copy endogenous retroviral element mapped to human Chromosome 1 at q42. A polymorphic Hin dIII site defines two different allelic forms of the genomic locus, The HRES-1/1 probe [5.5 kilobases (kb)] anneals to three polymorphic fragments and three genotypes can be differentiated: I, 5.5 kb fragment only; II, 3.7 kb and 1.8 kb fragments only; and III, all three polymorphic fragments, By cloning of the HRES-1 locus from homozygous type I and type II human DNA samples, the polymorphic Hin dIII site was identified as a G to C transition at position 653 of the long terminal repeat region. Family studies showed that Hin dIII genotypes of the HRES-1 locus are inherited in a Mendelian pattern, The relative frequency of genotype I with respect to genotype III was 3.1-fold lower in patients with SLE (14:40=0.35) in comparison to 100 ethnically matched control donors (47:43 = 1.09; P = 0.0084). Frequency of genotype I vs genotype II alleles was lower in SLE (68/ 52) than in normal donors (137/63; P=0.033), suggesting that a genotype I allele of the HRES-1 locus may be protective against SLE. Western blot seroreactivity with recombinant HRES-1/p28 was noted in 4/14 (29%) of genotype I patients and 13/19 (68%) of genotype III patients (P