國家衛生研究院 NHRI:Item 3990099045/10488
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    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/10488


    题名: Protein truncating variants at the cholesteryl ester transfer protein gene and risk for coronary heart disease
    作者: Nomura, A;Won, HH;Khera, AV;Takeuchi, F;Ito, K;McCarthy, S;Emdin, CA;Klarin, D;Natarajan, P;Zekavat, SM;Gupta, N;Peloso, GM;Borecki, IB;Teslovich, TM;Asselta, R;Duga, S;Merlini, PA;Correa, A;Kessler, T;Wilson, JG;Bown, MJ;Hall, AS;Braund, PS;Carey, DJ;Murray, MF;Kirchner, HL;Leader, JB;Lavage, DR;Manus, JN;Hartzel, DN;Samani, NJ;Schunkert, H;Marrugat, J;Elosua, R;McPherson, R;Farrall, M;Watkins, H;Juang, JJ;Hsiung, CA;Lin, SY;Wang, JS;Consortium, TAICHI;Tada, H;Kawashiri, MA;Inazu, A;Yamagishi, M;Katsuya, T;Nakashima, E;Nakatochi, M;Yamamoto, K;Yokota, M;Momozawa, Y;Rotter, JI;Lander, ES;Rader, DJ;Danesh, JN;Ardissino, D;Gabriel, SB;Willer, CJ;Abecasis, G;Saleheen, D;Kubo, M;Kato, N;Chen, YI;Dewey, F;Kathiresan, S
    贡献者: Division of Biostatistics and Bioinformatics
    摘要: Rationale: Therapies which inhibit cholesteryl ester transfer protein (CETP) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human deoxyribonucleic acid 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 one Japanese-specific PTV in 27,561 participants from three 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 female; 1 in 975 participants carried a PTV at the CETP gene. Compared to non-carriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (HDL-C; effect size, 22.6 mg/dL; 95% confidence interval [CI], 18 to 27; P < 1.0x10-4), lower low-density lipoprotein cholesterol (LDL-C; -12.2 mg/dL; 95% CI, -23 to -0.98; P = 0.033), and lower triglycerides (-6.3%; 95% CI, -12 to -0.22, P = 0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% CI, 0.54 to 0.90; P = 5.1x10-3). Conclusions: Compared with non-carriers, carriers of PTV at CETP displayed higher HDL-C, lower LDL-C, lower triglycerides, and lower risk for CHD.
    日期: 2017-06
    關聯: Circulation Research. 2017 Jun;121(1):81-88.
    Link to: http://dx.doi.org/10.1161/circresaha.117.311145
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0009-7330&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000403914900012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85020786942
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