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

• Published in: Journal of diabetes investigation Vol. 10; no. 6; pp. 1447 - 1453
• Main Authors: Onuma, Hiroshi, Kawamura, Ryoichi, Tabara, Yasuharu, Yamashita, Masakatsu, Ohashi, Jun, Kawasaki, Eiji, Imagawa, Akihisa, Yamada, Yuya, Chujo, Daisuke, Takahashi, Kenji, Suehiro, Tadashi, Takata, Yasunori, Osawa, Haruhiko, Makino, Hideichi
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.11.2019; John Wiley and Sons Inc; Wiley
• Subjects: Alleles; Autoimmune diseases; Autophagy; BACH2; Basic-Leucine Zipper Transcription Factors - genetics; Biomarkers - analysis; Case-Control Studies; CLEC16A; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - pathology; Female; Follow-Up Studies; Gene frequency; Genes; Genetic Predisposition to Disease; Genomes; Genotype; Genotype & phenotype; Glucose; Histocompatibility antigen HLA; Hospitals; Humans; Insulin; Insulin - metabolism; Insulin‐triggered type 1 diabetes; Lectins, C-Type - genetics; Lymphocytes; Male; Middle Aged; Monosaccharide Transport Proteins - genetics; Original; Pathogenesis; Patients; Polymorphism, Single Nucleotide; Prognosis; Single-nucleotide polymorphism; Statistical analysis; Studies; White people; Japan; CLEC16A; Insulin-triggered type 1 diabetes; BACH2
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.13057

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. We analyzed 13 type 1 diabetes susceptible single‐nucleotide polymorphisms in the six insulin‐triggered type 1 diabetes and compared them with those in controls and patients with type 2 diabetes to clarify the genetic background of insulin‐triggered patients. The possibility that the risk variants of BACH2 and CLEC16A could contribute to the development of insulin‐triggered type 1 diabetes cannot be excluded.