Combinations of HLA-DPB1 and HLA-DQB1 alleles determine susceptibility to early-onset myasthenia gravis in Japan.
HLA class II alleles in the DQA1, DQB1, DRB1, and DPB1 genes were investigated in Japanese patients with myasthenia gravis (MG) by digestion of polymerase chain reaction amplified DNAs with allele specific restriction endonucleases (PCR-RFLP). A significantly higher frequency of DQB1*03, which includes *0301, *0302, *0303 and determines the serological DQ3 specificity, was observed in female patients less than 30 years in age at onset of disease compared with healthy controls (90.5 vs. 53.2%). This study also confirms the high incidence of DPB1*0201 in early-onset female patients compared to the controls (85.7 vs. 40.3%). Moreover, 81.0% of the early onset female patients were found to carry both DQB1*03 and DPB1*0201, compared to 17.7% of the controls. Since DQB1*03 and DPB1*0201 are not in linkage disequilibrium, both these alleles are supposed to be synergistically involved in disease development in early-onset female MG. In contrast, no obvious association of HLA-DQA1, DQB1, DRB1 and DPB1 alleles with either late-onset patients or patients with thymoma was observed. Clearly, the genetic background of Japanese females with early onset MG is different from that of other patients with MG.
Horiki
T
T
Department of Internal Medicine IV, Tokai University School of Medicine, Kanagawa, Japan.
Inoko
H
H
Moriuchi
J
J
Ichikawa
Y
Y
Arimori
S
S
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment; D012737:Sex Factors; D013945:Thymoma / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D013953:Thymus Neoplasms / Q000150:complications / Q000453:epidemiology / 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; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains