Distribution of HLA class II alleles among Scandinavian patients with systemic lupus erythematosus (SLE): an increased risk of SLE among non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes?
HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB1*03,DRB3*0101,DQA1*0501,DQB1*0201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA1*0501, which is in linkage disequilibrium with DRB1*03 as well as DRB1*11,12 (DR5). An increased frequency of DRB1*11,12 was observed (RR = 1.89, ns). No association with DRB1*15,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB1*03 class II heterozygotes), the cases homozygous for DRB1*03,DQA1*0501,DQB1*0201, known to be in linkage disequilibrium with the complement allele C4A*Q0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB1*03,DQA1*0501,DQB1*0201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE.
Skarsvåg
S
S
University of Trondheim, Department of Immunology, Trondheim Regional Hospital, Norway.
Hansen
K E
KE
Holst
A
A
Moen
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012306:Risk; D012537:Scandinavian and Nordic Countries
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553515:HLA-DRB1*12:12 antigen; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes