Krischer Jeffrey P, Liu Xiang, Lernmark Åke, Hagopian William A, Rewers Marian J, She Jin-Xiong, Toppari Jorma, Ziegler Anette-G, Akolkar Beena
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
Diabetes. 2017 Dec;66(12):3122-3129. doi: 10.2337/db17-0261. Epub 2017 Sep 13.
This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, gene (rs1004446_A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium (T1DGC). The risk of progression to T1D was not different among those with or without a family history of T1D ( = 0.39) or HLA-DR-DQ genotypes ( = 0.74). Age at developing multiple autoantibodies (hazard ratio = 0.96 per 1-month increase in age; 95% CI 0.95, 0.97; < 0.001) and the type of first autoantibody (when more than a single autoantibody was the first-appearing indication of seroconversion [ = 0.006]) were statistically significant. Female sex was also a significant risk factor ( = 0.03). Three single nucleotide polymorphisms were associated with increased diabetes risk (rs10517086_A [ = 0.03], rs1534422_G [ = 0.006], and rs2327832_G [ = 0.03] in ) and one with decreased risk (rs1004446_A in [ = 0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.
本文旨在确定在出现两种或更多种与糖尿病相关的自身抗体后，与自身免疫风险相关的因素是否仍然显著，并继续影响青少年糖尿病环境决定因素（TEDDY）研究中自身抗体阳性儿童的1型糖尿病（T1D）风险。纳入的特征包括多种自身抗体阳性时的年龄、性别、选定的高危HLA-DR-DQ基因型、与患T1D的家庭成员的关系、血清转化时的自身抗体、基因（rs1004446_A）以及1型糖尿病遗传协会（T1DGC）鉴定的非HLA基因多态性。有或没有T1D家族病史的人群进展为T1D的风险没有差异（P = 0.39），HLA-DR-DQ基因型之间也没有差异（P = 0.74）。出现多种自身抗体时的年龄（风险比 = 年龄每增加1个月为0.96；95%置信区间0.95，0.97；P < 0.001）以及第一种自身抗体的类型（当不止一种自身抗体是血清转化的首次出现指征时[P = 0.006]）具有统计学意义。女性也是一个显著的风险因素（P = 0.03）。三种单核苷酸多态性与糖尿病风险增加相关（rs10517086_A[P = 0.03]、rs1534422_G[P = 0.006]以及rs2327832_G[P = 0.03]），一种与风险降低相关（rs1004446_A[P = 0.006]）。TEDDY数据表明，非HLA基因多态性在自身免疫起始阶段可能发挥与自身免疫出现后进展为T1D时不同的作用。这些关联的强度可能与所研究人群的年龄以及高危HLA-DR-DQ亚型有关。
Zotero 插件
