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. 2009 Apr;58(4):1028-33.
doi: 10.2337/db08-1179. Epub 2009 Feb 2.

Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?

Andrea K Steck  1 , Weiming Zhang, Teodorica L Bugawan, Katherine J Barriga, Alan Blair, Henry A Erlich, George S Eisenbarth, Jill M Norris, Marian J Rewers
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Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?

Andrea K Steck et al. Diabetes. 2009 Apr.

"VSports最新版本" Abstract

Objective: Specific alleles of non-HLA genes INS, CTLA-4, and PTPN22 have been associated with type 1 diabetes. We examined whether some of these alleles influence development of islet autoimmunity or progression from persistent islet autoimmunity to type 1 diabetes in children with high-risk HLA-DR,DQ genotypes VSports手机版. .

Research design and methods: Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,449 young children carrying HLA-DR,DQ genotypes associated with type 1 diabetes V体育安卓版. Of those, 112 have developed islet autoimmunity (persistent autoantibodies to insulin, GAD65, and/or IA-2), and 47 of these have progressed to type 1 diabetes. The influence of polymorphisms of INS(-23Hph1), CTLA-4(T17A), and PTPN22(R620W) on development of persistent islet autoimmunity and progression to type 1 diabetes was evaluated by parametric models and by survival analyses. .

Results: PTPN22(R620W) allele T was associated with development of persistent islet autoimmunity (hazard ratio 1. 83 [95% CI 1. 27-2. 63]) controlling for ethnicity, presence of HLA-DR3/4,DQB1*0302, and having a first-degree relative with type 1 diabetes. Survival analyses showed a significantly (P = 0. 002) higher risk of persistent islet autoimmunity by age 10 years for the TT genotype (27. 3%) than for the CT or CC genotype (7. 9 and 5. 3%, respectively). Cumulative risk of persistent islet autoimmunity was slightly higher (P = 0. 02) for the INS(-23Hph1) AA genotype (7. 8%) than for the AT or TT genotype (4 V体育ios版. 2 and 6. 4% risk by age 10 years, respectively). .

Conclusions: Whereas the HLA-DR3/4,DQB1*0302 genotype had a dramatic influence on both development of islet autoimmunity and progression to type 1 diabetes, the PTPN22(R620W) T allele significantly influences progression to persistent islet autoimmunity in the DAISY cohort VSports最新版本. .

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Figures

FIG. 1.
FIG. 1.
Cumulative risk of development of persistent islet autoimmunity (calendar age) by PTPN22 genotypes (A) and cumulative risk of progression from persistent islet autoimmunity to type 1 diabetes (follow-up time since first islet autoimmunity positivity) by PTPN22 genotypes (B) were estimated by survival analyses.
FIG. 2.
FIG. 2.
A: Cumulative risk of development of persistent islet autoimmunity (calendar age) by PTPN22 genotypes was estimated by survival analyses and stratified by high-risk HLA-DR3/4,DQB1*0302. B: Cumulative risk of development of persistent islet autoimmunity (calendar age) by INS genotypes was estimated by survival analyses.
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