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Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity
Authors:Claudio Magistrelli  Ella Samoilova  Rajeev K Agarwal  Katalin Banki  Pasquale Ferrante  Adrian Vladutiu  Paul E Phillips  A Perl
Institution:(1) Departments of Medicine, Microbiology and Immunology, and Pathology State University of New York Health Science Center, College of Medicine, SUNY HSC, 750 East Adams Street, Syracuse, NY 13210, USA e-mail:perla@hscsyr.edu, Tel.: +1-315-4644194, Fax: +1-315-4644176, US;(2) University of Milan, 20148 Milan, Italy, IT;(3) SUNY and Buffalo General Hospital, Buffalo, NY 14203, USA, US
Abstract: 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<0.025). These data raise the possibility that the HRES-1 element or a gene in linkage disequilibrium with this genomic locus may influence autoimmunity in SLE. Received: 20 February 1999 / Revised: 15 April 1999
Keywords:  HRES-1  Endogenous retroviral element  Sle
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