Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
Department of Diabetes, Endocrine and Metabolic Disease, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan.
J Diabetes Investig. 2019 Nov;10(6):1447-1453. doi: 10.1111/jdi.13057. Epub 2019 May 14.
AIM/INTRODUCTION: Insulin administration was found to trigger type 1 diabetes in six Japanese type 2 diabetes patients with type 1 diabetes high-risk human leukocyte antigen class II and the class I allele of the insulin gene variable number tandem repeat genotype. The objective of the present study was to assess the contribution of non-human leukocyte antigen single-nucleotide polymorphisms (SNPs) to the risk of developing insulin-triggered type 1 diabetes.
We genotyped 13 type 1 diabetes susceptible SNPs in six patients and compared them with those in Japanese controls (Hap Map3-JPT). The SNPs that showed statistically significant results were further analyzed using non-diabetic control participants and participants with type 2 diabetes at the Ehime University Hospital.
The risk allele frequency of BACH2 rs3757247 in the six patients was significantly more frequent than that in 86 Japanese controls (P = 0.038). No significant difference in the allele frequency was observed in the other SNPs. This result was confirmed by the findings that the risk allele frequency of BACH2 in the six patients was significantly higher than that in the non-diabetic control participants (n = 179) and type 2 diabetes with or without insulin treatment (n = 154 or n = 152; P = 0.035, 0.034 or 0.037, respectively). Despite being statistically not significant, the six patients were all homozygous for the CLEC16A rs12708716 risk allele and five were homozygous for the CLEC16A rs2903692 risk allele.
In addition to type 1 diabetes high-risk human leukocyte antigen class II and the class I allele of the insulin gene variable number tandem repeat genotype, the possibility that the risk variants of BACH2 and CLEC16A could contribute to the development of insulin-triggered type 1 diabetes cannot be excluded.
目的/引言：在 6 名具有 1 型糖尿病高危人类白细胞抗原 II 类和胰岛素基因可变数串联重复基因型 I 类等位基因的日本 2 型糖尿病患者中，发现胰岛素给药可引发 1 型糖尿病。本研究的目的是评估非人类白细胞抗原单核苷酸多态性（SNP）对胰岛素引发 1 型糖尿病风险的贡献。
我们对 6 名患者中的 13 个 1 型糖尿病易感 SNP 进行了基因分型，并将其与日本对照（Hap Map3-JPT）进行了比较。在日本爱媛大学医院的非糖尿病对照参与者和 2 型糖尿病参与者中进一步分析了显示统计学显著结果的 SNP。
6 名患者中 BACH2 rs3757247 的风险等位基因频率明显高于 86 名日本对照者（P=0.038）。其他 SNP 的等位基因频率无显著差异。这一结果得到了以下发现的证实：6 名患者中 BACH2 的风险等位基因频率明显高于非糖尿病对照参与者（n=179）和有或无胰岛素治疗的 2 型糖尿病患者（n=154 或 n=152；P=0.035、0.034 或 0.037）。尽管统计学上无显著性，但 6 名患者均为 CLEC16A rs12708716 风险等位基因的纯合子，5 名患者为 CLEC16A rs2903692 风险等位基因的纯合子。
除了 1 型糖尿病高危人类白细胞抗原 II 类和胰岛素基因可变数串联重复基因型 I 类等位基因外，BACH2 和 CLEC16A 的风险变异体也有可能导致胰岛素引发的 1 型糖尿病，这一点不能排除。
