Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees.
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.
Moser
K L
KL
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Neas
B R
BR
Salmon
J E
JE
Yu
H
H
Gray-McGuire
C
C
Asundi
N
N
Bruner
G R
GR
Fox
J
J
Kelly
J
J
Henshall
S
S
Bacino
D
D
Dietz
M
M
Hogue
R
R
Koelsch
G
G
Nightingale
L
L
Shaver
T
T
Abdou
N I
NI
Albert
D A
DA
Carson
C
C
Petri
M
M
Treadwell
E L
EL
James
J A
JA
Harley
J B
JB
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