PCSK9 genetic variants and risk of type 2 diabetes a mendelian randomisation study

doi:10.1016/S2213-8587(16)30396-5

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Tyck till om SwePub Sök här!

Sökning: onr:"20223669" > PCSK9 genetic varia...

1 av 1
Föregående post
Nästa post
Till träfflistan

PCSK9 genetic variants and risk of type 2 diabetes a mendelian randomisation study

Schmidt, Amand F. (författare)

Swerdlow, Daniel I. (författare)

Holmes, Michael V. (författare)

(utgivare)

ELSEVIER SCIENCE INC 2017
2017
Engelska.
Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587. ; 5:2, 97-105

swepub:Mat__t

Abstract Ämnesord

Stäng

Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.

Hitta via bibliotek

The Lancet Diabetes and Endocrinology (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

1 av 1
Föregående post
Nästa post
Till träfflistan

Hitta mer i SwePub

Av författaren/redakt...: Schmidt, Amand F ...; Swerdlow, Daniel ...; Holmes, Michael ...; Patel, Riyaz S.; Fairhurst-Hunter ...; Lyall, Donald M.; visa fler...; Hartwig, Fernand ...; Horta, Bernardo ...; Hypponen, Elina; Power, Christine; Moldovan, Max; van Iperen, Erik; Hovingh, G. Kees; Demuth, Ilja; Norman, Kristina; Steinhagen-Thies ...; Demuth, Juri; Bertram, Lars; Liu, Tian; Coassin, Stefan; Willeit, Johann; Kiechl, Stefan; Willeit, Karin; Mason, Dan; Wright, John; Morris, Richard; Wanamethee, Goya; Whincup, Peter; Ben-Shlomo, Yoav; McLachlan, Stela; Price, Jackie F.; Kivimaki, Mika; Welch, Catherine; Sanchez-Galvez, ...; Marques-Vidal, P ...; Nicolaides, Andr ...; Panayiotou, Andr ...; Onland-Moret, N. ...; van der Schouw, ...; Matullo, Giusepp ...; Fiorito, Giovann ...; Guarrera, Simone ...; Sacerdote, Carlo ...; Wareham, Nichola ...; Langenberg, Clau ...; Scott, Robert; Luan, Jian'an; Bobak, Martin; Malyutina, Sofi ...; Pajak, Andrzej; Kubinova, Ruzena; Tamosiunas, Abdo ...; Pikhart, Hynek; Husemoen, Lise L ...; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Simonsen, Kennet ...; Cooper, Jackie; Humphries, Steve ...; Brilliant, Murra ...; Kitchner, Terrie; Hakonarson, Hako ...; Carrell, David S ...; McCarty, Catheri ...; Kirchner, H. Les ...; Larson, Eric B.; Crosslin, David ...; de Andrade, Mari ...; Roden, Dan M.; Denny, Joshua C.; Carty, Cara; Hancock, Stephen; Attia, John; Holliday, Elizab ...; Donnell, Martin ...; Yusuf, Salim; Chong, Michael; Pare, Guillaume; van der Harst, P ...; Said, M. Abdulla ...; Eppinga, Ruben N ...; Verweij, Niek; Snieder, Harold; Christen, Tim; Mook-Kanamori, D ...; Gustafsson, Stef ...; Lind, Lars; Ingelsson, Erik; Pazoki, Raha; Franco, Oscar; Hofman, Albert; Uitterlinden, An ...; Dehghan, Abbas; Teumer, Alexande ...; Baumeister, Seba ...; Doerr, Marcus; Lerch, Markus M.; Voelker, Uwe; Voelzke, Henry; Ward, Joey; Pell, Jill P.; Smith, Daniel J.; Meade, Tom; Maitland-van der ...; Baranova, Ekater ...; Young, Robin; Ford, Ian; Campbell, Archie; Padmanabhan, San ...; Bots, Michiel L.; Grobbee, Diederi ...; Froguel, Philipp ...; Thuillier, Dorot ...; Balkau, Beverley; Bonnefond, Ameli ...; Cariou, Bertrand; Smart, Melissa; Bao, Yanchun; Kumari, Meena; Mahajan, Anubha; Ridker, Paul M.; Chasman, Daniel ...; Reiner, Alex P.; Lange, Leslie A.; Ritchie, Marylyn ...; Asselbergs, Folk ...; Casas, Juan-Pabl ...; Keating, Brendan ...; Preiss, David; Hingorani, Aroon ...; Sattar, Naveed; visa färre...

Av lärosätet: Swepub_uni:_t

Sök utanför SwePub

Sök vidare i:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se