Human leukocyte antigen-A24 and -DQA1*0301 in Japanese insulin-dependent diabetes mellitus: independent contributions to susceptibility to the disease and additive contributions to acceleration of beta-cell destruction.
The aim of this study is to identify insulin-dependent diabetes mellitus (IDDM)-susceptible HLA antigens in IDDM patients who do not have established risk allele, HLA-DQA1*0301, and analyze relationship of these HLA antigens and the degree of beta-cell destruction. In 139 Japanese IDDM patients and 158 normal controls, HLA-A, -C, -B, -DR and -DQ antigens were typed. Serum C-peptide immunoreactivity response (deltaCPR) to a 100-g oral glucose load < or = 0.033 nmol/l was regarded as complete beta-cell destruction. All 14 patients without HLA-DQA1*0301 had HLA-A24, whereas only 35 of 58 (60.3%) normal controls without HLA-DQA1*0301 and only 72 of 125 (57.6%) IDDM patients with HLA-DQA1*0301 had this antigen (Pc = 0.0256 and Pc = 0.0080, respectively). DeltaCPR in IDDM patients with both HLA-DQA1*0301 and HLA-A24 (0.097 +/- 0.163 nmol/L, mean +/- SD, n = 65) were lower than in IDDM patients with HLA-DQA1*0301 only (0.219 +/- 0.237 nmol/L, n = 45, P < 0.0001) and in IDDM patients with HLA-A24 only (0.187 +/- 0.198 nmol/L, n = 14, P = 0.0395). These results indicate that both HLA-DQA1*0301 and HLA-A24 contribute susceptibility to IDDM independently and accelerate beta-cell destruction in an additive manner.
Nakanishi
K
K
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
Kobayashi
T
T
Murase
T
T
Naruse
T
T
Nose
Y
Y
Inoko
H
H
D000293:Adolescent; D000328:Adult; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D015234:HLA-A Antigens / Q000032:analysis*; D059871:HLA-A24 Antigen; D006683:HLA-DQ Antigens / Q000032:analysis*; D059848:HLA-DQ alpha-Chains; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D006680:HLA Antigens; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen