Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age‐specific effects of cis‐regulatory haplotypes at 17q12‐q21

Ayabe, Tadayuki; Fukami, Maki; Ogata, Tsutomu; Kawamura, Tomoyuki; Urakami, Tatsuhiko; Kikuchi, Nobuyuki; Yokota, Ichiro; Ihara, Kenji; Takemoto, Kana; Mukai, Tokuo; Nishii, Aki; Kikuchi, Tohru; Mori, Tetsuo; Shimura, Naoto; Sasaki, Goro; Kizu, Rika; Takubo, Noriyuki; Soneda, Shun; Fujisawa, Takao; Takaya, Ryuzo; Kizaki, Zenro; Kanzaki, Sho; Hanaki, Keiichi; Matsuura, Nobuo; Kasahara, Yoshihito; Kosaka, Kitaro; Takahashi, Tomohiro; Minamitani, Kanshi; Matsuo, Seiichiro; Mochizuki, Hidetaka; Kobayashi, Kenichi; Koike, Akemi; Horikawa, Reiko; Teno, Shinichi; Tsubouchi, Kohji; Mochizuki, Takahiro; Igarashi, Yutaka; Amemiya, Shin; Sugihara, Shigetaka; Diabetes, Adolescent

doi:10.1111/dme.13175

Cited by 13 publications

(15 citation statements)

References 19 publications

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“…A recent study performed by the present author group indicated a significant role for SNPs in INS and CTLA4 genes in the development of Type 1 diabetes in Japanese children . The results of this recent study together with those of the present study indicate that, immune functional variants of the HLA , INS , CTLA4 and FUT2 genes, are contributory risk factors for Type 1 diabetes in an ethnicity‐independent manner.…”

Section: Discussionsupporting

confidence: 78%

FUT2 non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

et al. 2016

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Section: Discussionsupporting

confidence: 78%

FUT2 non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

et al. 2016

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“…In a previous study, we reported a significantly higher odds ratio of IDDM2 in Japanese patients with type 1 diabetes than in Caucasian patients with type 1 diabetes . Ayabe et al . recently reported a high odds ratio for IDDM2 using SNP rs689 in Japanese patients with type 1 diabetes, which prompted us to again compare the odds ratio for the rs689 genotype between Japanese and Caucasian patients with type 1 diabetes, and the results are shown in Table .…”

Section: Discussionmentioning

confidence: 79%

“…The SNPs, rs3757247 and rs11755527, which are in tight linkage disequilibrium (LD), have been reported to be associated with type 1 diabetes in Caucasian individuals. Ayabe et al . confirmed the association of rs3757247 in Japanese individuals with childhood‐onset type 1 diabetes.…”

Section: Discussionmentioning

confidence: 82%

“…assembled a multicenter study group in order to carry out large‐scale studies of Japanese individuals, and confirmed several type 1 diabetes susceptible loci that were also reported in Caucasians. Ayabe et al . genotyped 63 susceptibility variants in >400 Japanese childhood‐onset autoimmune type 1 diabetes patients, and found 10 risk alleles that were significantly more frequent in type 1 diabetes patients than in non‐diabetic individuals.…”

Section: Introductionmentioning

confidence: 99%

“…Ikegami et al 19 assembled a multicenter study group in order to carry out large-scale studies of Japanese individuals, and confirmed several type 1 diabetes susceptible loci that were also reported in Caucasians. Ayabe et al 20 genotyped 63 susceptibility variants in >400 Japanese childhood-onset autoimmune type 1 diabetes patients, and found 10 risk alleles that were significantly more frequent in type 1 diabetes patients than in non-diabetic individuals. In the present study, we analyzed 13 type 1 diabetes susceptible SNPs, and compared them with those in controls and patients with type 2 diabetes clarify the genetic background of insulin-triggered type 1 diabetes patients.…”

Section: Introductionmentioning

confidence: 99%

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

Onuma

Kawamura

Tabara

et al. 2019

J of Diabetes Invest

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Aim/IntroductionInsulin 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 MethodsWe 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.ResultsThe 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.ConclusionsIn 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.

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Emerging insights on the role of gasdermins in infection and inflammatory diseases

Tang

Zheng

et al. 2020

Clin & Trans Imm

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The gasdermins, family of pore-forming proteins, are emerging key regulators of infection, autoinflammation and antitumor immunity. Multiple studies have recently characterised their crucial roles in driving pyroptosis, a lytic pro-inflammatory type of cell death. Additionally, gasdermins also act as key effectors of NETosis, secondary necrosis and apoptosis. In this review, we will address current understanding of the mechanisms of gasdermin activation and further describe the protective and detrimental roles of gasdermins in host defence and autoinflammatory diseases. These data suggest that gasdermins play a prominent role in innate immunity and autoinflammatory disorders, thereby providing potential new therapeutic avenues for the treatment of infection and autoimmune disease.

show abstract

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age‐specific effects of cis‐regulatory haplotypes at 17q12‐q21

Cited by 13 publications

References 19 publications

FUT2 non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

FUT2 non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

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

Emerging insights on the role of gasdermins in infection and inflammatory diseases

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