[Relationship between autoantibodies and HLA-DQ genotypes in patients with type 1 diabetes mellitus].
OBJECTIVE
To explore the relationship between the 3 islet autoantibodies, i.e., glutamic acid decarboxylase antibody (GADA), protein-tyrosine-phosphatase-2 autoantibody (IA-2A), and insulin autoantibody (IAA), and human leukocyte HLA-DQ genotypes in the patients with type 1 diabetes mellitus (T1DM).


METHODS
Peripheral blood samples were collected from 495 T1DM patients and 376 healthy controls. Radioligand assay was used to detect the levels of GADA and IA-2A. Seventy-one of the 495 T1DM patients with insulin treatment less than 14 days underwent radioligand assay to measure the IAA level. 338 TIDM patients, including 187 antibodies-positive and 151 antibodies-negative patients, and 278 healthy controls underwent PCR and sequencing so as to examine the genetic polymorphism of HLA-DQ.


RESULTS
(1) The frequencies of DQA1*03-DQB1 *0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes in the T1DM patients were 32.6%, 14.1% and 10.2% respectively, all significantly higher than those in the controls (21.9%, 3.5%, and 2.9% respectively, all P < 0.01), however, the frequency of DQA1*0102-DQB1*0602 haplotype in the T1DM patients was 1.7%, significantly lower than that in the controls (5.3%, P < 0.05). (2) The GADA positive rates of in the T;DM patients with DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype were 55.8% and 65.5% respectively, both significantly higher than those of the T1DM patients without DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (41.0% and 40.3%, respectively P < 0.05 or P < 0.01), and the IA-2A positive rate of the T1DM patients with DQA1*03-DQB1*0303 haplotype was 27.0%, significantly higher than that of the T1DM patients without DQA1*03-DQB1*0303 haplotype (7.9%, P < 0.01), there were no significant differences in GADA and IA-2A positivity between the T1DM patients with and without DQA1*03-DQB1*0302 haplotype (48.5% vs 43.9% and 24.2% vs 15.4%, both P > 0.05). The GADA positivity rate of the T1DM patients with DQA1*0102-DQB1 *0602 haplotype was 16.7%, significantly lower than those patients without DQA1*0102-DQB1 *0602 haplotype (45.9%, P < 0.05). There was no significant difference in IAA level between those patients with and without susceptible DQ alleles and haplotypes (P > 0.05).


CONCLUSIONS
GADA is associated with HLA-DQA1*05-DQB1*0201 and DQA1*03-DQB1*0401 haplotypes, and IA-2A is associated with DQA1*03-DQB1 *0303 haplotype.
Department of Endocrinology and Metabolism, Second Xiangya Hospital, Diabetes Center, Institute of Metabolism and Endocrinology, Central South University, Changsha 410011, China.
Jian-ping
JP
Wang
Chi
C
Zhang
Jian
J
Lin
Ying
Y
Yuan
Hai-feng
HF
Zhou
Gan
G
Huang
Min
M
Zhou
Zhi-guang
ZG
Zhou
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017027:Protein Tyrosine Phosphatases / Q000276:immunology
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D007330:Insulin Antibodies; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase