Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome.
To better define the genetic factors that predispose to primary Sjögren's syndrome (SS), we have used polymerase chain reaction in combination with oligonucleotide probe hybridization and DNA sequencing to analyze HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles in Caucasoid (California), Japanese (Tokyo), and Chinese (Shanghai and Beijing) SS patients. In comparison to local controls in each region, we found: 1) increased frequency of the predicted haplotype HLA-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 in Caucasoid patients (p < 0.001); 2) increased frequency of the predicted haplotype HLA-DRB1*0405-DRB4*0101-DQA1*0301-DQB1*0401 in Japanese patients (p < 0.05); 3) increased frequency of the predicted haplotype DRB1*0803-DQA1*0103-DQB1*0601 in Chinese patients (p < 0.05); and 4) no statistically significant association with DPB1 alleles in any group, although an increased number of Caucasoid and Japanese SS patients possessed DPB1*0301. Comparison of DNA sequences for the three disease-associated haplotypes in these ethnic groups revealed a shared region of predicted amino acids from positions 58 to 69 in the first domain of HLA-DQB1. These results extend previous studies by demonstrating that no single class II allele was associated with 1 degree SS in the different ethnic groups. However, a shared amino acid motif in the DQB1 first domain was present in each disease-associated haplotype.
Kang
H I
HI
Department of Immunology and Rheumatology, Scripps Research Institute, La Jolla, CA 92037.
Fei
H M
HM
Saito
I
I
Sawada
S
S
Chen
S L
SL
Yi
D
D
Chan
E
E
Peebles
C
C
Bugawan
T L
TL
Erlich
H A
HA
D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D005787:Gene Frequency; D005802:Genes, MHC Class II; D006682:HLA-DP Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D012859:Sjogren's Syndrome / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics*
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens