An extensive screen of the HLA region reveals an independent association of HLA class I and class II with susceptibility for systemic lupus erythematosus.
OBJECTIVE
The association of systemic lupus erythematosus (SLE) with the human leucocyte antigen (HLA) region is well known. In this study, we analysed the involvement of the HLA region in susceptibility for SLE in a stable founder, Caucasian population of SLE patients.


METHODS
We performed an extensive screen of the entire HLA region on 103 SLE patients and family-based controls. Both single locus association analysis and haplotype sharing analysis were performed. The Additional Disease Locus Test (ADLT) was applied to examine the nature of the observed associations and to distinguish true causal associations from associations due to linkage disequilibrium (LD).


RESULTS
Significant associations were observed at markers in the HLA class I, class II, and class III regions using both haplotype sharing and single locus methods. The haplotype sharing methods revealed the most significant difference at marker D6S1666 in the HLA class II region (p(HSS) = 0.00037, p(CROSS) = 1.7 x 10(-5)). The most significant result for single locus association was shown at marker D6S265 in the HLA class I region (p = 0.00019). The ADLT demonstrated that these markers represent independent associations.


CONCLUSIONS
HLA class I, class II, and class III are associated with SLE, but only class I and class II contribute independently to increased risk of SLE.
Martens
H A
HA
Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. h.a.martens@int.umcg.nl
Nolte
I M
IM
van der Steege
G
G
Schipper
M
M
Kallenberg
C G M
CG
Te Meerman
G J
GJ
Bijl
M
M
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D055815:Young Adult
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I