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Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies
We performed exome-wide association studies to identify single nucleotide polymorphisms that either influence fasting plasma glucose level or blood hemoglobin A(1c) content or confer susceptibility to type 2 diabetes mellitus in Japanese. Exome-wide association studies were performed with the use of...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655215/ https://www.ncbi.nlm.nih.gov/pubmed/29113320 http://dx.doi.org/10.18632/oncotarget.19287 |
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author | Yamada, Yoshiji Sakuma, Jun Takeuchi, Ichiro Yasukochi, Yoshiki Kato, Kimihiko Oguri, Mitsutoshi Fujimaki, Tetsuo Horibe, Hideki Muramatsu, Masaaki Sawabe, Motoji Fujiwara, Yoshinori Taniguchi, Yu Obuchi, Shuichi Kawai, Hisashi Shinkai, Shoji Mori, Seijiro Arai, Tomio Tanaka, Masashi |
author_facet | Yamada, Yoshiji Sakuma, Jun Takeuchi, Ichiro Yasukochi, Yoshiki Kato, Kimihiko Oguri, Mitsutoshi Fujimaki, Tetsuo Horibe, Hideki Muramatsu, Masaaki Sawabe, Motoji Fujiwara, Yoshinori Taniguchi, Yu Obuchi, Shuichi Kawai, Hisashi Shinkai, Shoji Mori, Seijiro Arai, Tomio Tanaka, Masashi |
author_sort | Yamada, Yoshiji |
collection | PubMed |
description | We performed exome-wide association studies to identify single nucleotide polymorphisms that either influence fasting plasma glucose level or blood hemoglobin A(1c) content or confer susceptibility to type 2 diabetes mellitus in Japanese. Exome-wide association studies were performed with the use of Illumina Human Exome-12 DNA Analysis or Infinium Exome-24 BeadChip arrays and with 11,729 or 8635 subjects for fasting plasma glucose level or blood hemoglobin A(1c) content, respectively, or with 14,023 subjects for type 2 diabetes mellitus (3573 cases, 10,450 controls). The relation of genotypes of 41,265 polymorphisms to fasting plasma glucose level or blood hemoglobin A(1c) content was examined by linear regression analysis. After Bonferroni's correction, 41 and 17 polymorphisms were significantly (P < 1.21 × 10(−6)) associated with fasting plasma glucose level or blood hemoglobin A(1c) content, respectively, with two polymorphisms (rs139421991, rs189305583) being associated with both. Examination of the relation of allele frequencies to type 2 diabetes mellitus with Fisher's exact test revealed that 87 polymorphisms were significantly (P < 1.21 × 10(−6)) associated with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that four polymorphisms (rs138313632, rs76974938, rs139012426, rs147317864) were significantly (P < 1.44 × 10(−4)) associated with type 2 diabetes mellitus, with rs138313632 and rs139012426 also being associated with fasting plasma glucose and rs76974938 with blood hemoglobin A(1c). Five polymorphisms—rs139421991 of CAT, rs189305583 of PDCL2, rs138313632 of RUFY1, rs139012426 of LOC100505549, and rs76974938 of C21orf59—may be novel determinants of type 2 diabetes mellitus. |
format | Online Article Text |
id | pubmed-5655215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56552152017-11-06 Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies Yamada, Yoshiji Sakuma, Jun Takeuchi, Ichiro Yasukochi, Yoshiki Kato, Kimihiko Oguri, Mitsutoshi Fujimaki, Tetsuo Horibe, Hideki Muramatsu, Masaaki Sawabe, Motoji Fujiwara, Yoshinori Taniguchi, Yu Obuchi, Shuichi Kawai, Hisashi Shinkai, Shoji Mori, Seijiro Arai, Tomio Tanaka, Masashi Oncotarget Research Paper We performed exome-wide association studies to identify single nucleotide polymorphisms that either influence fasting plasma glucose level or blood hemoglobin A(1c) content or confer susceptibility to type 2 diabetes mellitus in Japanese. Exome-wide association studies were performed with the use of Illumina Human Exome-12 DNA Analysis or Infinium Exome-24 BeadChip arrays and with 11,729 or 8635 subjects for fasting plasma glucose level or blood hemoglobin A(1c) content, respectively, or with 14,023 subjects for type 2 diabetes mellitus (3573 cases, 10,450 controls). The relation of genotypes of 41,265 polymorphisms to fasting plasma glucose level or blood hemoglobin A(1c) content was examined by linear regression analysis. After Bonferroni's correction, 41 and 17 polymorphisms were significantly (P < 1.21 × 10(−6)) associated with fasting plasma glucose level or blood hemoglobin A(1c) content, respectively, with two polymorphisms (rs139421991, rs189305583) being associated with both. Examination of the relation of allele frequencies to type 2 diabetes mellitus with Fisher's exact test revealed that 87 polymorphisms were significantly (P < 1.21 × 10(−6)) associated with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that four polymorphisms (rs138313632, rs76974938, rs139012426, rs147317864) were significantly (P < 1.44 × 10(−4)) associated with type 2 diabetes mellitus, with rs138313632 and rs139012426 also being associated with fasting plasma glucose and rs76974938 with blood hemoglobin A(1c). Five polymorphisms—rs139421991 of CAT, rs189305583 of PDCL2, rs138313632 of RUFY1, rs139012426 of LOC100505549, and rs76974938 of C21orf59—may be novel determinants of type 2 diabetes mellitus. Impact Journals LLC 2017-07-17 /pmc/articles/PMC5655215/ /pubmed/29113320 http://dx.doi.org/10.18632/oncotarget.19287 Text en Copyright: © 2017 Yamada et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Yamada, Yoshiji Sakuma, Jun Takeuchi, Ichiro Yasukochi, Yoshiki Kato, Kimihiko Oguri, Mitsutoshi Fujimaki, Tetsuo Horibe, Hideki Muramatsu, Masaaki Sawabe, Motoji Fujiwara, Yoshinori Taniguchi, Yu Obuchi, Shuichi Kawai, Hisashi Shinkai, Shoji Mori, Seijiro Arai, Tomio Tanaka, Masashi Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title | Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title_full | Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title_fullStr | Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title_full_unstemmed | Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title_short | Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies |
title_sort | identification of five genetic variants as novel determinants of type 2 diabetes mellitus in japanese by exome-wide association studies |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655215/ https://www.ncbi.nlm.nih.gov/pubmed/29113320 http://dx.doi.org/10.18632/oncotarget.19287 |
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