دورية أكاديمية
Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
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edsbas BASE edsbas.452D8B68 904 3 Academic Journal academicJournal 903.687927246094 |
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W</searchLink><br /><searchLink fieldCode="AR" term="%22Patel%2C+Riyaz+S%22">Patel, Riyaz S</searchLink><br /><searchLink fieldCode="AR" term="%22Keating%2C+Brendan+J%22">Keating, Brendan J</searchLink><br /><searchLink fieldCode="AR" term="%22Sattar%2C+Naveed%22">Sattar, Naveed</searchLink><br /><searchLink fieldCode="AR" term="%22Houlston%2C+Richard%22">Houlston, Richard</searchLink><br /><searchLink fieldCode="AR" term="%22Casas%2C+Juan+P%22">Casas, Juan P</searchLink><br /><searchLink fieldCode="AR" term="%22Hingorani%2C+Aroon+D%22">Hingorani, Aroon D</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => BMC cardiovascular disorders, London : BioMed Central, 2019, vol. 19, no. 1, 240, p. 1-10 ; eISSN 1471-2261 ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2019 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => LAEI VL (Lithuanian Institute of Agrarian Economics Virtual Library) / LAEI VB (Lietuvos agrarinės ekonomikos institutasvirtualią biblioteką) ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Genetic+association+studies%22">Genetic association studies</searchLink><br /><searchLink fieldCode="DE" term="%22LDL-cholesterol%22">LDL-cholesterol</searchLink><br /><searchLink fieldCode="DE" term="%22Mendelian+randomisation%22">Mendelian randomisation</searchLink><br /><searchLink fieldCode="DE" term="%22Phenome-wide+association+scan%22">Phenome-wide association scan</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. 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[0] => Array
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[TitleFull] => BMC cardiovascular disorders, London : BioMed Central, 2019, vol. 19, no. 1, 240, p. 1-10 ; eISSN 1471-2261
[Type] => main
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