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Titel:

Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease.

Dokumenttyp:
Journal Article; Meta-Analysis; Article
Autor(en):
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;...     »
Abstract:
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 thegene may provide insight into the efficacy of CETP inhibition.To test whether protein-truncating variants (PTVs) at thegene were associated with plasma lipid levels and CHD.We sequenced the exons of thegene 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 ofPTV carrier status with both plasma lipids and CHD. Among 58 469 participants withgene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at thegene. Compared with noncarriers, carriers of PTV athad higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; <1.0×10), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; =0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; =0.043).PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; =5.1×10).Compared with noncarriers, carriers of PTV atdisplayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD.
Zeitschriftentitel:
Circ Res
Jahr:
2017
Band / Volume:
121
Heft / Issue:
1
Seitenangaben Beitrag:
81-88
Sprache:
eng
Volltext / DOI:
doi:10.1161/CIRCRESAHA.117.311145
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/28506971
Print-ISSN:
0009-7330
TUM Einrichtung:
Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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