Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis

Hoke, M.; Speidl, Walter S.; Schillinger, Martin; Minar, Erich; Zehetmayer, Sonja; Schönherr, M; Wagner, Oswald; Mannhalter, Christine

doi:10.1111/j.1365-2362.2012.02669.x

Cited by 26 publications

(23 citation statements)

References 23 publications

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“…A similar result was found in patients with balloon angioplasty of the superficial femoral artery [34]. The C5 rs17611 GG genotype was found associated with increased C5a plasma level and represents a risk factor of adverse cardiovascular outcome in male patients with carotid atherosclerosis [35]. In patients who underwent combined aortic valve replacement and coronary artery bypass grafting, the administration of an antibody against C5 (the precursor of C5a) was associated with decreased mortality at 180-day follow-up [36].…”

Section: Serum C5a Level and The Prognosis Of Atherosclerosissupporting

confidence: 64%

Role of C5a-C5aR axis in the development of atherosclerosis

Ren

et al. 2014

Sci. China Life Sci.

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Complement component 5a (C5a) is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor, C5, on activation of the complement cascade. C5a is quickly metabolised by carboxypeptidases, forming the less-potent C5a desArg. C5a and C5a desArg interact with their receptors (C5aR and C5L2), which results in a number of effects which are essential to the immune response. C5a has a broad range of biological effects throughout the human body because the widespread expression of C5a receptors throughout the human organs enables C5a and C5a desArg to elicit a broad range of biological effects. Recently, accumulating evidence in humans and experimental animal models shows that the C5a-C5aR axis is involved in the development of atherosclerosis lesions. The absence or blockade of C5aRs greatly reduces the formation of atherosclerotic lesions or wire-injury-induced neointima formation in atherosclerosis-prone mice. Serum C5a level was related to the major adverse cardiovascular events in patients with advanced atherosclerosis and those with drug-eluting stent implantation. Thus, the C5a-C5aR axis may be a significant pathogenic driver of arteriosclerotic vascular disease, making C5a-C5aR inhibition an attractive therapeutic strategy.

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Section: Serum C5a Level and The Prognosis Of Atherosclerosissupporting

confidence: 64%

Role of C5a-C5aR axis in the development of atherosclerosis

Ren

et al. 2014

Sci. China Life Sci.

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“…Chai et al (4) show an association (p , 0.007) of rs17611 (and its linked set) with periodontal disease; Woehrl et al (5) show an association (p , 0.002) of rs17611 with outcome in pneumococcal meningitis; Hoke et al (6) show an association (p , 0.01) of rs17611 with adverse cardiovascular outcome; and Greisenegger et al (7) show an association (p , 0.005) of rs17611 with risk for ischemic stroke. Together, these linkages provided a strong rationale to explore the functional consequences of the rs17611 SNP on C5 activities, the major focus of our paper.…”

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confidence: 99%

“…N.D., LD for SNP is not determined. 6 I n their Comment, Messemaker et al discuss genetic data that show that block 2 within the TRAF1-C5 locus is a risk for rheumatoid arthritis (RA), while block 3 is not associated. We acknowledge these data, which illustrate that, when taken in isolation, block 3 does not impact disease risk.…”

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confidence: 99%

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Comment on “Functional Analysis of a Complement Polymorphism (rs17611) Associated with Rheumatoid Arthritis”

Messemaker

Toes

Mikkers

et al. 2015

The Journal of Immunology

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“…Woehrl et al found that the C5 rs17611 is associated with unfavorable disease outcome in patients with bacterial meningitis 18 . Recently, Giles et al showed that individuals homozygously (GG) expressing the C5 rs17611 allele exhibit increased C5a and decreased C5 in plasma 19 . In this study, they explored the functional consequences of an SNP (rs17611) encoding a V802I polymorphism in C5.…”

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confidence: 99%

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients

Weng

Zheng

et al. 2016

Arq. Neuro-Psiquiatr.

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The complement system has been confirmed to play an increasingly important role in ischemic stroke (IS). This study aimed to determine whether the single-nucleotide polymorphism of the complement 5 (C5) gene independently influences the occurrence, severity, and long-term outcome of IS in Chinese patients. Methods C5 rs17611 genetic variants were investigated in 494 IS patients and 330 control individuals .Ischemic stroke was classiﬁed into subtypes and patients were assessed 90 days post-stroke with the modified Rankin Scale to determine stroke outcome. Results The presence of C5 polymorphism was associated with the incidence of large artery atherosclerosis (LAA)-subtype IS (n =2 00; p = 0.031), which even persisted after adjustment for covariates (OR = 1.518; 95%CI = 1.093–2.018; p = 0.013). However, no association was found between genotypes and the severity and outcome of stroke (p = 0.978; p = 0.296). Conclusions The C5 polymorphism might contribute to the risk of LAA-subtype IS independently of other known risk predictors.

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Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis

Abstract: The C5 rs17611 GG genotype is associated with increased C5a plasma levels and represents a risk factor for adverse cardiovascular outcome in male patients with carotid atherosclerosis.

Cited by 26 publications

References 23 publications

Role of C5a-C5aR axis in the development of atherosclerosis

Role of C5a-C5aR axis in the development of atherosclerosis

Comment on “Functional Analysis of a Complement Polymorphism (rs17611) Associated with Rheumatoid Arthritis”

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients

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