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Title: Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: A Meta-analysis.
Authors: Lotta, Luca A
Sharp, Stephen J
Burgess, Stephen
Perry, John R B
Stewart, Isobel D
Willems, Sara M
Luan, Jian'an
Ardanaz, Eva
Arriola, Larraitz
Balkau, Beverley
Boeing, Heiner
Deloukas, Panos
Forouhi, Nita G
Franks, Paul W
Grioni, Sara
Kaaks, Rudolf
Key, Timothy J
Navarro, Carmen
Nilsson, Peter M
Overvad, Kim
Palli, Domenico
Panico, Salvatore
Quirós, Jose-Ramón
Riboli, Elio
Rolandsson, Olov
Sacerdote, Carlotta
Salamanca, Elena C
Slimani, Nadia
Spijkerman, Annemieke Mw
Tjonneland, Anne
Tumino, Rosario
van der A, Daphne L
van der Schouw, Yvonne T
McCarthy, Mark I
Barroso, Inês
O'Rahilly, Stephen
Savage, David B
Sattar, Naveed
Langenberg, Claudia
Scott, Robert A
Wareham, Nicholas J
metadata.dc.subject.mesh: ATP Binding Cassette Transporter, Subfamily G, Member 5
Cholesterol, LDL
Cohort Studies
Coronary Artery Disease
Diabetes Mellitus, Type 2
Drug Therapy, Combination
Genetic Association Studies
Genetic Variation
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Membrane Proteins
Membrane Transport Proteins
Middle Aged
Odds Ratio
Polymorphism, Genetic
Proprotein Convertase 9
Receptors, LDL
Issue Date: 2016
Abstract: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes. To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes. The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016. Low-density lipoprotein cholesterol-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR. Odds ratios (ORs) for type 2 diabetes and coronary artery disease. Low-density lipoprotein cholesterol-lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95% CI, 1.70-3.43]; P  In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.
metadata.dc.identifier.doi: 10.1001/jama.2016.14568
Appears in Collections:Producción 2020

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