Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset

被引：134

作者：

Kawabata, Y. ^{[1
]}

Ikegami, H. ^{[1
]}

Awata, T. ^{[2
]}

Imagawa, A. ^{[3
]}

Maruyama, T. ^{[4
]}

Kawasaki, E. ^{[5
]}

Tanaka, S. ^{[6
]}

Shimada, A. ^{[7
]}

Osawa, H. ^{[8
]}

Kobayashi, T. ^{[6
]}

Hanafusa, T. ^{[9
]}

Tokunaga, K. ^{[10
]}

Makino, H. ^{[11
]}

机构：

[1] Kinki Univ, Sch Med, Dept Endocrinol Metab & Diabet, Osaka 5898511, Japan

[2] Saitama Med Univ, Dept Endocrinol & Diabet, Saitama, Japan

[3] Osaka Univ, Dept Metab Med, Grad Sch Med, Osaka, Japan

[4] Saitama Social Insurance Hosp, Dept Internal Med, Saitama, Japan

[5] Nagasaki Univ, Hosp Med & Dent, Dept Metab Diabet & Clin Nutr, Nagasaki 852, Japan

[6] Univ Yamanashi, Dept Internal Med 3, Interdisciplinary Grad Sch Med & Engn, Yamanashi, Japan

[7] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan

[8] Ehime Univ, Grad Sch Med, Dept Mol & Genet Med, Matsuyama, Ehime 790, Japan

[9] Osaka Med Coll, Dept Internal Med 1, Osaka, Japan

[10] Univ Tokyo, Dept Human Genet, Grad Sch Med, Tokyo, Japan

[11] Takanoko Hosp, Ctr Diabet, Takanoka, Ehime, Japan

来源：

DIABETOLOGIA | 2009年 / 52卷 / 12期

关键词：

Fulminant type 1 diabetes; Genetics; HLA; Single nucleotide polymorphism; Slowly progressive type 1 diabetes; Susceptibility; Type; 1; diabetes; CLASS-II ALLELES; DQ HAPLOTYPES; ADULT-ONSET; MELLITUS; SUSCEPTIBILITY; ANTIBODIES; HUMANS; LOCI;

D O I：

10.1007/s00125-009-1539-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive. We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA. DRB1*0405-DQB1*0401, DRB1*0802-DQB1*0302 and DRB1*0901-DQB1*0303 were associated with acute-onset type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 genotype achieving the highest odds ratio of 42.7. DRB1*1501-DQB1*0602 and DRB1*1502-DQB1*0601 were negatively associated with acute-onset type 1 diabetes. A similar tendency was observed for slowly progressive type 1 diabetes. In contrast, only DRB1*0405-DQB1*0401 was associated with fulminant type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0405-DQB1*0401 genotype showing the highest odds ratio of 11.2. DRB1*0802-DQB1*0302, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 and DRB1*1501-DQB1*0602 were not associated with fulminant type 1 diabetes. The association of class I alleles and a panel of SNPs in an extended HLA region with fulminant type 1 diabetes was also different from that seen for the acute-onset and slowly progressive forms. The presence of both one and two susceptible haplotypes conferred susceptibility to slowly progressive type 1 diabetes, whereas the presence of two susceptible haplotypes was required to confer susceptibility to acute-onset and fulminant type 1 diabetes. These data suggest that HLA associations with fulminant type 1 diabetes are qualitatively different from those with other subtypes of type 1 diabetes, whereas the HLA contribution to slowly progressive type 1 diabetes is qualitatively similar to, but quantitatively different from, that in acute-onset type 1 diabetes.

引用

页码：2513 / 2521

页数：9

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