Combination of HLA-A24, -DQA1*03, and -DR9 contributes to acute-onset and early complete β-cell destruction in type 1 diabetes -: Longitudinal study of residual β-cell function

被引:42
作者
Nakanishi, Koji
Inoko, Hidetoshi
机构
[1] Toranomon Gen Hosp, Dept Endocrinol & Metab, Minato Ku, Tokyo 1058470, Japan
[2] Okinaka Mem Inst Med Res, Tokyo, Japan
[3] Tokai Univ, Dept Mol Life Sci, Div Mol Med Sci & Mol Med, Grad Sch Med, Kanagawa 2591100, Japan
关键词
D O I
10.2337/db05-1049
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To elucidate the genetic factors contributing to heterogeneity of the rate of beta-cell destruction in type 1 diabetes, we investigated the relationship between the time course of complete beta-cell loss and HLA class I and II alleles. HLA allele frequencies were also examined among subgroups classified by the mode of onset. The subjects were 266 type 1 diabetic patients (among whom 196 patients were studied longitudinally) and 136 normal control subjects. Earlier complete loss of beta-cell function was observed in patients who possessed both HLA-A24 and HLA-DQA1*03 and in patients who had HLA-DR9, compared with those without these HLA alleles (P = 0.0057 and 0.0093, respectively). Much earlier complete R-cell loss was observed in the patients who possessed all of HLA-A24, -DQA1*03, and -DR9 compared with the remaining patients (P = 0.0011). The combination of HLA-A24, -DQA1*03, and -DR9 showed a higher frequency in acute-onset than slow-onset type 1 diabetes (P = 0.0002). In contrast, HLA-DR2 was associated with a slower rate of progression to complete P-cell loss. These results indicate that the combination of HLA-A24, -DQA1*03, and -DR9 contributes to the acute-onset and early complete P-cell destruction, whereas HLA-DR2 has a protective effect against complete beta-cell loss in type 1 diabetes.
引用
收藏
页码:1862 / 1868
页数:7
相关论文
共 41 条
[31]  
Raddrizzani L, 1997, J IMMUNOL, V159, P703
[32]  
REIJONEN H, 2005, JOSLINS DIABETES MEL, P355
[33]   Identification of children with early onset and high incidence of anti-islet autoantibodies [J].
Robles, DT ;
Eisenbarth, GS ;
Wang, TB ;
Erlich, HA ;
Bugawan, TL ;
Babu, SR ;
Barriga, K ;
Norris, JM ;
Hoffman, M ;
Klingensmith, G ;
Yu, LP ;
Rewers, M .
CLINICAL IMMUNOLOGY, 2002, 102 (03) :217-224
[34]  
RONNINGEN KS, 1992, HLA 1991, P713
[35]  
Schlesselman J.J., 1982, Case-control studies: design, conduct, analysis, V2
[36]   Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults:: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden [J].
Schölin, A ;
Björklund, L ;
Borg, H ;
Arnqvist, H ;
Björk, E ;
Blohmé, G ;
Bolinder, J ;
Eriksson, JW ;
Gudbjörnsdottir, S ;
Nyström, L ;
Östman, J ;
Karlsson, AF ;
Sundkvist, G .
JOURNAL OF INTERNAL MEDICINE, 2004, 255 (03) :384-391
[37]  
Sosenko JM, 2004, DIABETES, V53, pA425
[38]   Association of HLA-DR, DQ genotype with different beta-cell functions at IDDM diagnosis in Japanese children [J].
Sugihara, S ;
Sakamaki, T ;
Konda, S ;
Murata, A ;
Wataki, K ;
Kobayashi, Y ;
Minamitani, K ;
Miyamoto, S ;
Sasaki, N ;
Niimi, H .
DIABETES, 1997, 46 (11) :1893-1897
[39]  
TERASAKI PI, 1978, AM J CLIN PATHOL, V69, P103
[40]   ANTIBODIES TO GLUTAMIC-ACID DECARBOXYLASE REVEAL LATENT AUTOIMMUNE DIABETES-MELLITUS IN ADULTS WITH A NON-INSULIN-DEPENDENT ONSET OF DISEASE [J].
TUOMI, T ;
GROOP, LC ;
ZIMMET, PZ ;
ROWLEY, MJ ;
KNOWLES, W ;
MACKAY, IR .
DIABETES, 1993, 42 (02) :359-362