title: Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcgamma receptors (FcgammaR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambdas > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcgammaRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.
authors.affiliation: Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Moser
authors.forename: B R
authors.initials: BR
authors.lastname: Neas
authors.forename: J E
authors.initials: JE
authors.lastname: Salmon
authors.forename: H
authors.initials: H
authors.lastname: Yu
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authors.initials: C
authors.lastname: Gray-McGuire
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authors.initials: N
authors.lastname: Asundi
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authors.initials: GR
authors.lastname: Bruner
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authors.lastname: Fox
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authors.lastname: Henshall
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authors.lastname: Koelsch
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authors.lastname: Shaver
authors.forename: N I
authors.initials: NI
authors.lastname: Abdou
authors.forename: D A
authors.initials: DA
authors.lastname: Albert
authors.forename: C
authors.initials: C
authors.lastname: Carson
authors.forename: M
authors.initials: M
authors.lastname: Petri
authors.forename: E L
authors.initials: EL
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mesh_terms: D000818:Animals; D044383:Black People / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D051379:Mice; D010375:Pedigree; D001741:Black or African American