Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives.
The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes was higher (P < 0.05-0.01) but DQA1*0102-DQB1*0602 haplotype was lower (P < 0.01) in T1D patients. DQA1*03 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA1*03-DQB1*0303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA1*0102-DQB1*0602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA1*03-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.
Wang
J-P
JP
Department of Endocrinology, Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhou
Z-G
ZG
Lin
J
J
Huang
G
G
Zhang
C
C
Yang
L
L
Yuan
Y
Y
Zhou
H-F
HF
Zhou
M
M
Hou
C
C
Zhou
W-D
WD
Peng
H
H
Hagopian
W A
WA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005190:Family; D005260:Female; D005787:Gene Frequency / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D007330:Insulin Antibodies / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D007330:Insulin Antibodies; D008562:Membrane Glycoproteins; C024211:islet cell antibody; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase