Confirmation of genetic linkage between human systemic lupus erythematosus and chromosome 1q41.
OBJECTIVE
Genetic susceptibility to systemic lupus erythematosus (SLE) is undoubtedly complex and, presumably, involves multiple loci. Linkage of SLE to D1S229 at chromosome 1q41 has been previously reported in a cohort of 52 affected sibpairs. The present study sought to confirm this reported linkage in an independent cohort of 127 extended multiplex SLE pedigrees containing 107 affected sibpairs.


METHODS
Genotype data were collected for D1S229 and 18 flanking microsatellite markers spanning chromosome 1q32-1q42. Analyses of genotype data included a model-based logarithm of odds (LOD) score approach, affected sibpair analyses, and transmission disequilibrium tests.


RESULTS
A maximum LOD score of 1.46 was found with D1S229 in a subgroup of 78 European American pedigrees, with additional support from multiple markers clustered around D1S229. Increased allele sharing in affected siblings was most significant at D1S2616, particularly in European Americans (P = 0.0005), followed by D1S229 (P = 0.002), D1S490 (P = 0.028), and D1S1605 (P = 0.037). Although linkage in a subgroup of 40 African American pedigrees was not suggested by the analyses of any marker tested in the chromosomal region surrounding D1S229, a maximum LOD score of 3.03 was found with D1S3462, mapped 15 centimorgans distal to D1S229.


CONCLUSIONS
Our linkage analysis results in European Americans at D1S229 are remarkably similar to those previously reported. That at least 1 genetic effect near this locus is important for susceptibility to lupus should now be generally accepted, and efforts to identify the gene are thereby justified.
Moser
K L
KL
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Gray-McGuire
C
C
Kelly
J
J
Asundi
N
N
Yu
H
H
Bruner
G R
GR
Mange
M
M
Hogue
R
R
Neas
B R
BR
Harley
J B
JB
D044383:Black People / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D014481:United States; D001741:Black or African American