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J Diabetes Investig. 2019 Apr 10. doi: 10.1111/jdi.13057. [Epub ahead of print]

Variants in the BACH2 and CLEC16A gene might be associated with susceptibility to insulin-triggered type 1 diabetes.

Author information

1
Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
2
Department of Diabetes, Endocrine and Metabolic Disease, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan.
3
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
4
Department of Immunology, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
5
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
6
Department of Diabetes and Endocrinology, Shin-Koga Hospital, Kurume, Fukuoka, Japan.
7
Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Osaka, Japan.
8
Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan.
9
Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo, Japan.
10
Department of Internal Medicine, Diabetes Division, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.
11
Department of Diabetes, Kochi Takasu Hospital, Kochi, Kochi, Japan.
12
Shiraishi Hospital Diabetes Center, Imabari, Ehime, Japan.

Abstract

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

BACH2 ; CLEC16A ; Insulin-triggered type 1 diabetes

PMID:
30970177
DOI:
10.1111/jdi.13057
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