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Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies

We have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)–cholesterol, or low density lipoprotein (LDL)–cholesterol or confer susceptibility to hypertriglyceridemia, hypo–HDL-chole...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503585/
https://www.ncbi.nlm.nih.gov/pubmed/28473662
http://dx.doi.org/10.18632/oncotarget.17159
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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 have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)–cholesterol, or low density lipoprotein (LDL)–cholesterol or confer susceptibility to hypertriglyceridemia, hypo–HDL-cholesterolemia, or hyper–LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo–HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper–LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly (P < 1.21 × 10(−6)) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol–, or LDL-cholesterol–related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo–HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper–LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo–HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper–LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper–LDL-cholesterolemia, respectively.
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spelling pubmed-55035852017-07-11 Identification of eight genetic variants as novel determinants of dyslipidemia 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 have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)–cholesterol, or low density lipoprotein (LDL)–cholesterol or confer susceptibility to hypertriglyceridemia, hypo–HDL-cholesterolemia, or hyper–LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo–HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper–LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly (P < 1.21 × 10(−6)) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol–, or LDL-cholesterol–related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo–HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper–LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo–HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper–LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper–LDL-cholesterolemia, respectively. Impact Journals LLC 2017-04-17 /pmc/articles/PMC5503585/ /pubmed/28473662 http://dx.doi.org/10.18632/oncotarget.17159 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 eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title_full Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title_fullStr Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title_full_unstemmed Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title_short Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
title_sort identification of eight genetic variants as novel determinants of dyslipidemia in japanese by exome-wide association studies
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503585/
https://www.ncbi.nlm.nih.gov/pubmed/28473662
http://dx.doi.org/10.18632/oncotarget.17159
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