Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart DiseaseNovelty and Significance
dc.contributor.author | Nomura, Akihiro | |
dc.contributor.author | Won, Hong-Hee | |
dc.contributor.author | Khera, Amit V. | |
dc.contributor.author | Takeuchi, Fumihiko | |
dc.contributor.author | Ito, Kaoru | |
dc.contributor.author | McCarthy, Shane | |
dc.contributor.author | Emdin, Connor A. | |
dc.contributor.author | Klarin, Derek | |
dc.contributor.author | Natarajan, Pradeep | |
dc.contributor.author | Gupta, Namrata | |
dc.contributor.author | Peloso, Gina M. | |
dc.contributor.author | Borecki, Ingrid B. | |
dc.contributor.author | Teslovich, Tanya M. | |
dc.contributor.author | Asselta, Rosanna | |
dc.contributor.author | Duga, Stefano | |
dc.contributor.author | Merlini, Piera A. | |
dc.contributor.author | Correa, Adolfo | |
dc.contributor.author | Kessler, Thorsten | |
dc.contributor.author | Wilson, James G. | |
dc.contributor.author | Bown, Matthew J. | |
dc.contributor.author | Hall, Alistair S. | |
dc.contributor.author | Braund, Peter S. | |
dc.contributor.author | Carey, David J. | |
dc.contributor.author | Kirchner, H. Lester | |
dc.contributor.author | Leader, Joseph B. | |
dc.contributor.author | Lavage, Daniel R. | |
dc.contributor.author | Manus, J. Neil | |
dc.contributor.author | Hartze, Dustin N. | |
dc.contributor.author | Samani, Nilesh J. | |
dc.contributor.author | Schunkert, Heribert | |
dc.contributor.author | Marrugat, Jaume | |
dc.contributor.author | Elosua, Roberto | |
dc.contributor.author | McPherson, Ruth | |
dc.contributor.author | Farrall, Martin | |
dc.contributor.author | Watkins, Hugh | |
dc.contributor.author | Juang, Jyh-Ming J. | |
dc.contributor.author | Hsiung, Chao A. | |
dc.contributor.author | Lin, Shih-Yi | |
dc.contributor.author | Wang, Jun-Sing | |
dc.contributor.author | Tada, Hayato | |
dc.contributor.author | Kawashiri, Masa-aki | |
dc.contributor.author | Inazu, Akihiro | |
dc.contributor.author | Yamagishi, Masakazu | |
dc.contributor.author | Katsuya, Tomohiro | |
dc.contributor.author | Nakashima, Eitaro | |
dc.contributor.author | Nakatochi, Masahiro | |
dc.contributor.author | Yamamoto, Ken | |
dc.contributor.author | Yokota, Mitsuhiro | |
dc.contributor.author | Momozawa, Yukihide | |
dc.contributor.author | Rotter, Jerome I. | |
dc.contributor.author | Rader, Daniel J. | |
dc.contributor.author | Danesh, John | |
dc.contributor.author | Ardissino, Diego | |
dc.contributor.author | Gabriel, Stacey | |
dc.contributor.author | Willer, Cristen J. | |
dc.contributor.author | Abecasis, Goncalo R. | |
dc.contributor.author | Saleheen, Danish | |
dc.contributor.author | Kubo, Michiaki | |
dc.contributor.author | Kato, Norihiro | |
dc.contributor.author | Ida Chen, Yii-Der | |
dc.contributor.author | Dewey, Frederick E. | |
dc.contributor.author | Kathiresan, Sekar | |
dc.contributor.author | Zekavat, Seyedeh M. | |
dc.contributor.author | Murray, Michael F | |
dc.contributor.author | Lander, Eric Steven | |
dc.date.accessioned | 2018-06-28T17:47:06Z | |
dc.date.available | 2018-06-28T17:47:06Z | |
dc.date.issued | 2017-05 | |
dc.date.submitted | 2017-04 | |
dc.identifier.issn | 0009-7330 | |
dc.identifier.issn | 1524-4571 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116679 | |
dc.description.abstract | Rationale: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. Objective: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. Methods and Results: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). Conclusions: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD. | en_US |
dc.publisher | Ovid Technologies (Wolters Kluwer Health) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1161/CIRCRESAHA.117.311145 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart DiseaseNovelty and Significance | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Nomura, Akihiro et al. “Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease Novelty and Significance.” Circulation Research 121, 1 (May 2017): 81–88 © 2017 American Heart Association, Inc | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Zekavat, Seyedeh M. | |
dc.contributor.mitauthor | Murray, Michael F | |
dc.contributor.mitauthor | Lander, Eric Steven | |
dc.relation.journal | Circulation Research | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-06-28T13:04:05Z | |
dspace.orderedauthors | Nomura, Akihiro; Won, Hong-Hee; Khera, Amit V.; Takeuchi, Fumihiko; Ito, Kaoru; McCarthy, Shane; Emdin, Connor A.; Klarin, Derek; Natarajan, Pradeep; Zekavat, Seyedeh M.; Gupta, Namrata; Peloso, Gina M.; Borecki, Ingrid B.; Teslovich, Tanya M.; Asselta, Rosanna; Duga, Stefano; Merlini, Piera A.; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Carey, David J.; Murray, Michael F.; Kirchner, H. Lester; Leader, Joseph B.; Lavage, Daniel R.; Manus, J. Neil; Hartze, Dustin N.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Juang, Jyh-Ming J.; Hsiung, Chao A.; Lin, Shih-Yi; Wang, Jun-Sing; Tada, Hayato; Kawashiri, Masa-aki; Inazu, Akihiro; Yamagishi, Masakazu; Katsuya, Tomohiro; Nakashima, Eitaro; Nakatochi, Masahiro; Yamamoto, Ken; Yokota, Mitsuhiro; Momozawa, Yukihide; Rotter, Jerome I.; Lander, Eric S.; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Willer, Cristen J.; Abecasis, Goncalo R.; Saleheen, Danish; Kubo, Michiaki; Kato, Norihiro; Ida Chen, Yii-Der; Dewey, Frederick E.; Kathiresan, Sekar | en_US |
dspace.embargo.terms | N | en_US |
mit.license | OPEN_ACCESS_POLICY | en_US |