OBJECTIVE We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children). The presence of SNPs rs2476601 (PTPN22) and rs2292239 (ERBB3) demonstrated increased risk of both autoantibodies to insulin (IAA) only and GADA only. SNP rs689 (INS) was protective of IAA only, but not of GADA only. The rs3757247 (BACH2) SNP demonstrated increased risk of GADA only. Male sex, father or sibling as the diabetic proband, introduction of probiotics under 28 days of age, and weight at age 12 months were associated with IAA only, but only father as the diabetic proband and weight at age 12 months were associated with GADA only. Mother as the diabetic proband was not a significant risk factor. CONCLUSIONS These results show clear differences in the initiation of autoimmunity according to genetic factors and environmental exposures that give rise to IAA or GADA as the first appearing indication of autoimmunity.

中文翻译：

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遗传和环境相互作用会改变 6 岁时患糖尿病相关自身免疫的风险：TEDDY 研究。

目的 我们测试了胰岛自身抗体和 1 型糖尿病的遗传背景和选定的环境暴露之间的关联。研究设计和方法 对具有 HLA-DR 高危基因型的婴儿进行前瞻性随访，了解糖尿病相关自身抗体的情况。单核苷酸多态性 (SNP) 来自 Illumina 免疫芯片，环境暴露数据来自家长报告。儿童被跟踪至6岁。结果 胰岛素自身抗体出现早于 GAD 抗体 (GADA)，然后下降，而 GADA 发生率上升并保持不变（在 HLA-DR4 中显着，但在 DR3/3 儿童中不显着）。SNP rs2476601 (PTPN22) 和 rs2292239 (ERBB3) 的存在表明仅胰岛素 (IAA) 和仅 GADA 自身抗体的风险增加。SNP rs689 (INS) 仅对 IAA 具有保护作用，而不仅仅对 GADA 有保护作用。rs3757247 (BACH2) SNP 仅显示 GADA 风险增加。男性、父亲或兄弟姐妹作为糖尿病先证者、28 天以下益生菌的引入以及 12 个月时的体重仅与 IAA 相关，但只有父亲作为糖尿病先证者和 12 个月时的体重仅与 GADA 相关。母亲作为糖尿病先证者并不是一个显着的危险因素。结论 这些结果表明，根据遗传因素和环境暴露，自身免疫的启动存在明显差异，导致 IAA 或 GADA 作为自身免疫的第一个出现的迹象。