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

Wu, Hui; Weng, Yingfeng; Zheng, Lan; Li, Huanyin; Gong, Qiang; Fu, Yi; Zhao, Jing

doi:10.1590/0004-282x20160139

Cited by 6 publications

(4 citation statements)

References 22 publications

(14 reference statements)

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“…These include ten proteins (APCS, APOM, C1qA, C4BPA, CBP2, F2, FBLN1, IGKV1D-12, KLKB1, SERPINF2) that differentiate the cardioembolic vs. large-vessel stroke, six other proteins (AMBP, APOA4, FCN3, ITIH4, LBP, PF4) that differentiate the cardioembolic vs. lacunar stroke, and another six proteins (APOL1, C5, GPX3, GSN, H2AFJ, IGK) that differentiate the large-vessel vs. lacunar stroke (Table 3, Figure 3B). To the best of our knowledge, with the exception of C5, known to be associated with large-vessel stroke in a Chinese population [18], these differentiating proteins, weree not previously associated with a specific subtype of the ischemic stroke. These findings raise a possiblity that the ischemic stroke subtype-specific proteins can be exploited, most likely as a panel, in diagnosis and prognosis of outcomes, and possibly therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Sikora

Kupc

et al. 2019

IJMS

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Ischemic stroke induces brain injury via thrombotic or embolic mechanisms involving large or small vessels. Cystathionine β-synthase deficiency (CBS), an inborn error of metabolism, is associated with vascular thromboembolism, the major cause of morbidity and mortality in affected patients. Because thromboembolism involves the brain vasculature in these patients, we hypothesize that CBS deficiency and ischemic stroke have similar molecular phenotypes. We used label-free mass spectrometry for quantification of changes in serum proteomes in CBS-deficient patients (n = 10) and gender/age-matched unaffected controls (n = 14), as well as in patients with cardioembolic (n = 17), large-vessel (n = 26), or lacunar (n = 25) ischemic stroke subtype. In CBS-deficient patients, 40 differentially expressed serum proteins were identified, of which 18 were associated with elevated homocysteine (Hcy) and 22 were Hcy-independent. We also identified Hcy-independent differentially expressed serum proteins in ischemic stroke patients, some of which were unique to a specific subtype: 10 of 32 for cardioembolic vs. large-vessel, six of 33 for cardioembolic vs. lacunar, and six of 23 for large-vessel vs. lacunar. There were significant overlaps between proteins affected by CBS deficiency and ischemic stroke, particularly the cardioembolic subtype, similar to protein overlaps between ischemic stroke subtypes. Top molecular pathways affected by CBS deficiency and ischemic stroke subtypes included acute phase response signaling and coagulation system. Similar molecular networks centering on NFκB were affected by CBS deficiency and stroke subtypes. These findings suggest common mechanisms involved in the pathologies of CBS deficiency and ischemic stroke subtypes.

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Section: Discussionmentioning

confidence: 99%

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Sikora

Kupc

et al. 2019

IJMS

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“…Proteins act on pathogen opsonization in a cascade reaction and induce inflammation, which activates immune cells against the invading agent and assist in maintaining host homeostasis ( 44 ). Studies have confirmed that genetic mutations in complement genes, as well as modifications in their expression levels, are associated with development of several human disorders, such as schizophrenia ( 45 ), age-related macular degeneration ( 46 ), Alzheimer’s disease ( 47 ), myocardial infarction ( 48 ), and stroke ( 49 ). In addition, these events were also interrelated with susceptibility to several bacterial and viral infectious diseases, such as meningitis ( 50 , 51 ), leprosy ( 52 ), hepatitis B ( 53 ), and diseases caused by trypanosomatids: CD ( 22 ), VL ( 36 ), and CL ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review

et al. 2021

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BackgroundTrypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system − through classical, alternative and lectin pathways − plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.MethodsIn March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.ResultsTwelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.ConclusionThis systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.

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“… 43 Other studies indicated that rs17611, a missense polymorphism leading to a V802I change in C5, was associated with elevated C5a production, increased susceptibility to large artery atherosclerosis stroke, and poor cardiovascular outcome. 44 , 45 However, no current studies have explored the clinical relationship of C5 SNPs with the susceptibility and clinical prognosis of sepsis. In this study, our results indicated that rs2269067 polymorphism exerted protective effect against sepsis susceptibility, as indicated by significantly lower frequencies of the GC/CC genotypes or C allele in sepsis patients than in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Association of Complement 5 Genetic Polymorphisms with Sepsis and Sepsis-Induced Inflammatory Responses

Chen¹,

Lin²,

Liu³

et al. 2021

JIR

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Background: Complement 5 (C5) and C5a production play a pivotal role in the pathophysiology of sepsis. Strong evidence demonstrates an association of C5 gene polymorphisms with various inflammatory diseases. However, no current studies have explored the clinical relevance of C5 polymorphisms in sepsis. Methods: Two C5 gene polymorphisms, rs17611 and rs2269067, were identified by genotyping in 636 sepsis patients and 753 controls in a Han Chinese population. C5 gene expression was detected via quantitative real-time PCR. C5a and proinflammatory cytokine production was measured by enzyme-linked immunosorbent assay. An Annexin V apoptosis assay was performed to assess cell apoptosis. Results: Our results showed significantly lower frequencies of rs2269067 GC/CC genotypes or C allele in sepsis patients than healthy controls. The frequencies of rs17611 CC/CT genotypes or C allele were significantly overrepresented in both the septic shock and nonsurvivor subgroups. Patients with this sepsis-associated high-risk rs17611 C allele exhibited a significant increase in C5a, TNF-α and IL-6 production. However, no significant difference in C5a and downstream proinflammatory cytokine production was observed among patients with different rs2269067 genotypes. In addition, in vitro experiments showed an effect of recombinant C5a on enhancing LPS-stimulated IL-1β, IL-6 and TNF-α production and cell apoptosis in THP-1 monocytes. Conclusion:The rs2269067 polymorphism conferred protection against sepsis susceptibility. The rs17611 polymorphism was associated with increased C5a production, which ultimately potentiated the secretion of downstream proinflammatory cytokines and conferred susceptibility to sepsis progression and poor prognosis.

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

Cited by 6 publications

References 22 publications

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes

Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review

Investigation of Association of Complement 5 Genetic Polymorphisms with Sepsis and Sepsis-Induced Inflammatory Responses

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