X Zhang1, A Wang2,3, J Zhang1, M Singh4, D Liu1, Y Zuo2,3, L Wu1, M Song1, W Wang4, V Feigin5, Y Wang1, D Zheng1. 1. Department of Epidemiology and Health Statistics, School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China. 2. China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 4. School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia. 5. National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand.
Abstract
BACKGROUND AND PURPOSE: Elevated C-reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. METHODS: Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP-associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first-ever IS patients and 613 healthy controls. RESULTS: Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79-1.45) for rs876537, 0.99 (0.73-1.35) for rs1205 and 1.08 (0.71-1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP ≥2.0 mg/l was 2.19 (1.06-4.53) compared with <2.0 mg/l. The adjusted OR (95% CI) of IS per genetically predicted 10% higher CRP concentration, based on the three SNPs as the instruments, was 1.02 (0.94-1.11). Furthermore, similar results were obtained with adjusted ORs (95% CI) of 1.00 (0.88-1.13) and 1.04 (0.93-1.16), respectively, for large-artery atherosclerosis and small-artery occlusion per genetically predicted 10% higher CRP concentration. CONCLUSIONS: This Mendelian randomization study provides no clear support that elevated CRP concentration is causally associated with the risk of IS.
BACKGROUND AND PURPOSE: Elevated C-reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. METHODS: Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP-associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first-ever ISpatients and 613 healthy controls. RESULTS: Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79-1.45) for rs876537, 0.99 (0.73-1.35) for rs1205 and 1.08 (0.71-1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP ≥2.0 mg/l was 2.19 (1.06-4.53) compared with <2.0 mg/l. The adjusted OR (95% CI) of IS per genetically predicted 10% higher CRP concentration, based on the three SNPs as the instruments, was 1.02 (0.94-1.11). Furthermore, similar results were obtained with adjusted ORs (95% CI) of 1.00 (0.88-1.13) and 1.04 (0.93-1.16), respectively, for large-artery atherosclerosis and small-artery occlusion per genetically predicted 10% higher CRP concentration. CONCLUSIONS: This Mendelian randomization study provides no clear support that elevated CRP concentration is causally associated with the risk of IS.
Authors: Cristina Gallego-Fabrega; Elena Muiño; Jara Cárcel-Márquez; Laia Llucià-Carol; Miquel Lledós; Jesús M Martín-Campos; Natalia Cullell; Israel Fernández-Cadenas Journal: Int J Mol Sci Date: 2022-06-20 Impact factor: 6.208