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Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus
Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977841/ https://www.ncbi.nlm.nih.gov/pubmed/24709989 http://dx.doi.org/10.1371/journal.pone.0088602 |
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author | Kodama, Shinjiro Yamada, Tetsuya Imai, Junta Sawada, Shojiro Takahashi, Kei Tsukita, Sohei Kaneko, Keizo Uno, Kenji Ishigaki, Yasushi Oka, Yoshitomo Katagiri, Hideki |
author_facet | Kodama, Shinjiro Yamada, Tetsuya Imai, Junta Sawada, Shojiro Takahashi, Kei Tsukita, Sohei Kaneko, Keizo Uno, Kenji Ishigaki, Yasushi Oka, Yoshitomo Katagiri, Hideki |
author_sort | Kodama, Shinjiro |
collection | PubMed |
description | Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients (onset age <35 years) at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24.2-3 and 22q13.31-33, which have significant associations with early-onset Japanese T2DM. The associations were statistically significant by Fisher's exact tests with P values of 5.19×10(−3) and 1.81×10(−3) and odds ratios of 5.7 and 4.4 for 16q24.2-3 and 22q13.31-33, respectively. Furthermore, copy number variation (CNV) analysis of the whole genome using the CNV BeadChip system verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Our results suggest that the mechanism underlying induction of CNVs is involved in the pathogenesis of early-onset T2DM. Thus, copy number losses within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM. |
format | Online Article Text |
id | pubmed-3977841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39778412014-04-11 Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus Kodama, Shinjiro Yamada, Tetsuya Imai, Junta Sawada, Shojiro Takahashi, Kei Tsukita, Sohei Kaneko, Keizo Uno, Kenji Ishigaki, Yasushi Oka, Yoshitomo Katagiri, Hideki PLoS One Research Article Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients (onset age <35 years) at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24.2-3 and 22q13.31-33, which have significant associations with early-onset Japanese T2DM. The associations were statistically significant by Fisher's exact tests with P values of 5.19×10(−3) and 1.81×10(−3) and odds ratios of 5.7 and 4.4 for 16q24.2-3 and 22q13.31-33, respectively. Furthermore, copy number variation (CNV) analysis of the whole genome using the CNV BeadChip system verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Our results suggest that the mechanism underlying induction of CNVs is involved in the pathogenesis of early-onset T2DM. Thus, copy number losses within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM. Public Library of Science 2014-04-07 /pmc/articles/PMC3977841/ /pubmed/24709989 http://dx.doi.org/10.1371/journal.pone.0088602 Text en © 2014 Kodama et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kodama, Shinjiro Yamada, Tetsuya Imai, Junta Sawada, Shojiro Takahashi, Kei Tsukita, Sohei Kaneko, Keizo Uno, Kenji Ishigaki, Yasushi Oka, Yoshitomo Katagiri, Hideki Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title | Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title_full | Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title_fullStr | Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title_full_unstemmed | Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title_short | Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus |
title_sort | simultaneous copy number losses within multiple subtelomeric regions in early-onset type2 diabetes mellitus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977841/ https://www.ncbi.nlm.nih.gov/pubmed/24709989 http://dx.doi.org/10.1371/journal.pone.0088602 |
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