C5 Variant rs10985126 is Associated with Mortality in Patients with Symptomatic Coronary Artery Disease.

BACKGROUND

Complement component 5a (C5a) is a highly potent anaphylatoxin with a variety of pro-inflammatory effects. C5a contributes to progression of atherosclerosis and inhibition of the receptor (C5aR) might offer a therapeutic strategy in this regard. Single nucleotide polymorphisms (SNPs) of the C5 gene may modify protein expression levels and therefore function of C5a and C5aR. This study aimed to examine associations between clinically relevant C5a SNPs and the prognosis of patients with symptomatic coronary artery disease (CAD). Furthermore, we sought to investigate the influence of C5 SNPs on C5aR platelet surface expression and circulating C5a levels.

METHODS

C5 variants (rs25681, rs17611, rs17216529, rs12237774, rs41258306, and rs10985126) were analyzed in a consecutive cohort of 833 patients suffering from symptomatic coronary artery disease (CAD). Circulating C5a levels were determined in 116 patients whereas C5aR platelet surface expression was measured in 473 CAD patients. Endpoints included all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS). Homozygous carriers (HC) of the minor allele (rs10985126) showed significantly higher all-cause mortality than major allele carriers. While we could not find significant associations between rs10985126 allele frequency and C5aR platelet surfazl ce expression, significantly elevated levels of circulating C5a were found in HC of the minor allele of the respective genotype. rs17216529 allele frequency correlated with the composite combined endpoint and bleeding events. However, since the number of HC of the minor allele of this genotype was low, we cannot draw a robust conclusion about the observed associations.

CONCLUSION

In this study, we provide evidence for the prognostic relevance of rs10985126 in CAD patients. C5 rs10985126 may serve as a prognostic biomarker for risk stratification in high-risk CAD patients and consequently promote tailored therapies.

Informations de copyright

© 2021 Henes et al.

Déclaration de conflit d'intérêts

Dr Elke Schaeffeler report grants from DFG (grant number SCHW858/1-1/2), grants from Robert Bosch Stiftung, Stuttgart (Germany), during the conduct of the study; Dr Stefan Winter report grants from Robert Bosch Stiftung (Stuttgart, Germany), grants from DFG Germany (grant number SCHW858/1-2), during the conduct of the study; Professor Matthias Schwab report grants from DFG SCHW858/1-1/2, grants from Robert Bosch Stiftung, during the conduct of the study; grants from Green Cross WellBeing Co. Ltd., grants from Gilead Sciences Inc., grants from Agena Bioscience GmbH, grants from University Hospital Tuebingen, grants, non-financial support from Robert Bosch GmbH, outside the submitted work; and Pharmacogenetics and Genomics, Editor in Chief Drug Research, Editor in Chief Genome Medicine, Section Editor Honoraria for oral presentations at academically organised congresses and meetings, External Reviewer for Research Impact Fund Hong Kong, External Reviewer for EU Horizon 2020, External Reviewer for the Science Council of the Federal Government of Germany. Professor Tobias Geisler report grants from German Research Foundation (DFG), during the conduct of the study. The authors report no other conflicts of interest in this work.