title: Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity.
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.
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Magistrelli
authors.forename: E
authors.initials: E
authors.lastname: Samoilova
authors.forename: R K
authors.initials: RK
authors.lastname: Agarwal
authors.forename: K
authors.initials: K
authors.lastname: Banki
authors.forename: P
authors.initials: P
authors.lastname: Ferrante
authors.forename: A
authors.initials: A
authors.lastname: Vladutiu
authors.forename: P E
authors.initials: PE
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: Perl
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000097:blood; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D010375:Pedigree; D011110:Polymorphism, Genetic; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology; D020079:Terminal Repeat Sequences
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D001324:Autoantigens; D017931:DNA Primers; C096557:HRES-1 p28 protein, human retroviral element; D012191:Retroviridae Proteins