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Association of plasma C‐reactive protein with ischaemic stroke: a Mendelian randomization study
Author(s) -
Zhang X.,
Wang A.,
Zhang J.,
Singh M.,
Liu D.,
Zuo Y.,
Wu L.,
Song M.,
Wang W.,
Feigin V.,
Wang Y.,
Zheng D.
Publication year - 2020
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.14113
Subject(s) - mendelian randomization , medicine , confidence interval , odds ratio , single nucleotide polymorphism , snp , allele , c reactive protein , gastroenterology , genotype , genetics , genetic variants , biology , gene , inflammation
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.