<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients
Accumulating evidence has suggested that viral infection causes type 1 diabetes due to direct β-cell damage and the triggering of autoimmune reactivity to β cells. Here, we elucidated that the tyrosine kinase 2 <i>(Tyk2</i>) gene, encoding an interferon receptor signaling molecule, is re...
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doaj-3beda35cd9dd41bba0e5a08b0ff08bac2021-03-12T00:03:36ZengMDPI AGGenes2073-44252021-03-011240040010.3390/genes12030400<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes PatientsHitoe Mori0Hirokazu Takahashi1Keiichiro Mine2Ken Higashimoto3Kanako Inoue4Motoyasu Kojima5Shigetaka Kuroki6Takahisa Eguchi7Yasuhiro Ono8Sadataka Inuzuka9Hidenobu Soejima10Seiho Nagafuchi11Keizo Anzai12Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanDivison of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanEguchi Hospital, Saga 845-0032, JapanEguchi Hospital, Saga 845-0032, JapanDepartment of Internal Medicine, Kouhokai Takagi Hospital, Fukuoka 831-0016, JapanInuzuka Hospital, Saga 849-1311, JapanDivison of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanDivision of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, JapanAccumulating evidence has suggested that viral infection causes type 1 diabetes due to direct β-cell damage and the triggering of autoimmune reactivity to β cells. Here, we elucidated that the tyrosine kinase 2 <i>(Tyk2</i>) gene, encoding an interferon receptor signaling molecule, is responsible for virus-induced diabetes in mice, and its promoter variant confers a risk of type 1 diabetes in humans. This study investigated the relationship between a <i>TYK2</i> promoter variant <i>(TYK2PV)</i> and insulin secretion in type 2 diabetes patients. <i>TYK2PV</i> status was determined using direct DNA sequencing and its associations with fasting insulin, C-peptide, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated in type 2 diabetes patients without sulfonylurea or insulin medication. Of the 172 patients assessed, 18 (10.5%) showed <i>TYK2PV</i>-positivity. Their body mass index (BMI) was significantly lower than in those without the variant (23.4 vs. 25.4 kg/m<sup>2</sup>, <i>p</i> = 0.025). Fasting insulin (3.9 vs. 6.2 μIU/mL, <i>p</i> = 0.007), C-peptide (1.37 vs. 1.76 ng/mL, <i>p</i> = 0.008), and HOMA-IR (1.39 vs. 2.05, <i>p</i> = 0.006) were lower in those with than in those without the variant. Multivariable analysis identified that <i>TYK2PV</i> was associated with fasting insulin ≤ 5 μIU/mL (odds ratio (OR) 3.63, <i>p</i> = 0.025) and C-peptide ≤ 1.0 ng/mL (OR 3.61, <i>p</i> = 0.028), and also lower insulin resistance (HOMA-IR ≤ 2.5; OR 8.60, <i>p</i> = 0.042). <i>TYK2PV</i> is associated with impaired insulin secretion and low insulin resistance in type 2 diabetes. Type 2 diabetes patients with <i>TYK2PV</i> should be carefully followed in order to receive the appropriate treatment including insulin injections.https://www.mdpi.com/2073-4425/12/3/400n/a |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hitoe Mori Hirokazu Takahashi Keiichiro Mine Ken Higashimoto Kanako Inoue Motoyasu Kojima Shigetaka Kuroki Takahisa Eguchi Yasuhiro Ono Sadataka Inuzuka Hidenobu Soejima Seiho Nagafuchi Keizo Anzai |
spellingShingle |
Hitoe Mori Hirokazu Takahashi Keiichiro Mine Ken Higashimoto Kanako Inoue Motoyasu Kojima Shigetaka Kuroki Takahisa Eguchi Yasuhiro Ono Sadataka Inuzuka Hidenobu Soejima Seiho Nagafuchi Keizo Anzai <i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients Genes n/a |
author_facet |
Hitoe Mori Hirokazu Takahashi Keiichiro Mine Ken Higashimoto Kanako Inoue Motoyasu Kojima Shigetaka Kuroki Takahisa Eguchi Yasuhiro Ono Sadataka Inuzuka Hidenobu Soejima Seiho Nagafuchi Keizo Anzai |
author_sort |
Hitoe Mori |
title |
<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients |
title_short |
<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients |
title_full |
<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients |
title_fullStr |
<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients |
title_full_unstemmed |
<i>TYK2</i> Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients |
title_sort |
<i>tyk2</i> promoter variant is associated with impaired insulin secretion and lower insulin resistance in japanese type 2 diabetes patients |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-03-01 |
description |
Accumulating evidence has suggested that viral infection causes type 1 diabetes due to direct β-cell damage and the triggering of autoimmune reactivity to β cells. Here, we elucidated that the tyrosine kinase 2 <i>(Tyk2</i>) gene, encoding an interferon receptor signaling molecule, is responsible for virus-induced diabetes in mice, and its promoter variant confers a risk of type 1 diabetes in humans. This study investigated the relationship between a <i>TYK2</i> promoter variant <i>(TYK2PV)</i> and insulin secretion in type 2 diabetes patients. <i>TYK2PV</i> status was determined using direct DNA sequencing and its associations with fasting insulin, C-peptide, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated in type 2 diabetes patients without sulfonylurea or insulin medication. Of the 172 patients assessed, 18 (10.5%) showed <i>TYK2PV</i>-positivity. Their body mass index (BMI) was significantly lower than in those without the variant (23.4 vs. 25.4 kg/m<sup>2</sup>, <i>p</i> = 0.025). Fasting insulin (3.9 vs. 6.2 μIU/mL, <i>p</i> = 0.007), C-peptide (1.37 vs. 1.76 ng/mL, <i>p</i> = 0.008), and HOMA-IR (1.39 vs. 2.05, <i>p</i> = 0.006) were lower in those with than in those without the variant. Multivariable analysis identified that <i>TYK2PV</i> was associated with fasting insulin ≤ 5 μIU/mL (odds ratio (OR) 3.63, <i>p</i> = 0.025) and C-peptide ≤ 1.0 ng/mL (OR 3.61, <i>p</i> = 0.028), and also lower insulin resistance (HOMA-IR ≤ 2.5; OR 8.60, <i>p</i> = 0.042). <i>TYK2PV</i> is associated with impaired insulin secretion and low insulin resistance in type 2 diabetes. Type 2 diabetes patients with <i>TYK2PV</i> should be carefully followed in order to receive the appropriate treatment including insulin injections. |
topic |
n/a |
url |
https://www.mdpi.com/2073-4425/12/3/400 |
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