Effect of the PTPN22 and INS Risk Genotypes on the Progression to Clinical Type 1 Diabetes After the Initiation of β-Cell Autoimmunity

被引:23
作者
Lempainen, Johanna [1 ,2 ]
Hermann, Robert [1 ]
Veijola, Riitta [3 ]
Simell, Olli [2 ]
Knip, Mikael [4 ,5 ,6 ]
Ilonen, Jorma [7 ]
机构
[1] Univ Turku, Immunogenet Lab, Turku, Finland
[2] Univ Turku, Dept Pediat, Turku, Finland
[3] Univ Oulu, Dept Pediat, SF-90100 Oulu, Finland
[4] Tampere Univ Hosp, Dept Pediat, Tampere, Finland
[5] Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland
[6] Folkhalsan Res Ctr, Helsinki, Finland
[7] Univ Eastern Finland, Dept Clin Microbiol, Kuopio, Finland
基金
芬兰科学院;
关键词
LYMPHOID TYROSINE PHOSPHATASE; GENE VARIANT; INSULIN GENE; HUMAN THYMUS; CLASS-II; CHILDREN; POPULATION; ALLELES; DISEASE; LOCUS;
D O I
10.2337/db11-0386
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We set out to analyze the role of two major non-HLA gene polymorphisms associated with type 1 diabetes (T1D), PTPN22 1858C/T and insulin gene INS-23 A/T in progression to clinical T1D after the appearance of beta-cell autoimmunity. The study population comprised 249 children with HLA-associated T1D susceptibility. All subjects were persistently positive for at least one of the T1D-associated biochemically defined autoantibodies (insulin autoantibody, GAD antibody, or IA-2 antibody), and 136 subjects presented with T1D over a median follow-up of 4.3 years (range 0.0-12.5) after the appearance of the first autoantibody. The PTPN22 1858T allele was strongly associated with progression to T1D after the appearance of the first biochemically defined beta-cell autoantibody (hazard ratio 1.68 [95% CI 1.09-2.60], P = 0.02 Cox regression analysis, multivariate test), and the effect remained similar when analyzed after the appearance of the second autoantibody (P = 0.013), whereas INS-23 HphI AA genotype was not associated with progression to clinical diabetes after the appearance of the first or second autoantibody (P = 0.38 and P = 0.88, respectively). The effect of the INS risk genotype seems to be limited to the induction and early phases of beta-cell autoimmunity, but the PTPN22 1858T allele instead affects the initiation and late progression phase of diabetes-associated autoimmunity. Diabetes 61:963-966, 2012
引用
收藏
页码:963 / 966
页数:4
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