MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection

Túlio, Siumara; Faucz, Fábio R.; Werneck, Renata Iani; Olandoski, Márcia; Alexandre, Rodrigo Bertollo de; Boldt, Angelica Beate Winter; Pedroso, Fiona L.; Messias-Reason, Iara José de

doi:10.1016/j.humimm.2011.06.016

Cited by 33 publications

(25 citation statements)

References 27 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is therefore a plausible clinical and disease pathogenesis context for our findings. Finally, in support of the notion that lectin pathway complement activation may have a role in liver fibrosis, both MASP-2 [34] and MBL-2 [35] single nucleotide polymorphisms have been shown to correlate with the severity of liver fibrosis and outcomes in HCV-infected individuals. Taken together, the clinical and experimental evidence supports the notion that MASP-1 could be a driver of disease progression in HCV infection, and that innate immune responses may promote progression of HCVrelated disease in certain individuals.…”

Section: Discussionmentioning

confidence: 74%

Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Saeed

Baloch

Brown

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryMannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.

show abstract

Section: Discussionmentioning

confidence: 74%

Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Saeed

Baloch

Brown

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…In another study no effect of this mutation was observed on the MASP-2 levels; instead it was found that this mutation increases the MBL binding capacity of the MASP-2 protein 43. And finally, the rs12711521 SNP has been shown to be associated with high levels of MASP-244 as well as with susceptibility to such diseases as leprosy,45 hepatitis C,46 malaria,47 bacterial infections after orthotopic liver transplantation,48 Chagas disease49 and rheumatoid arthritis 50…”

Section: Discussionmentioning

confidence: 99%

Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke

Tsakanova

Stepanyan

Nahapetyan³

et al. 2017

J Clin Pathol

View full text Add to dashboard Cite

AimsThe aim of the current study was to assess the proteolytic activities of collectin-bound MASP-1 and MASP-2 in the blood of patients with ischaemic stroke, as well as the association of their six genetic polymorphisms (rs3203210, rs28945070, rs28945073 in MASP1 gene and rs2273343, rs12711521, rs147270785 in MASP2 gene) with this pathology.MethodsIn total, 250 patients and 300 healthy subjects were involved in this study. MBL-associated serine protease (MASP)-1 and MASP-2 activities were measured using in-house developed immunofluorescent and enzyme-linked immunosorbent assays, respectively. Sequence specific primer PCR was used to study the association of MASP1 and MASP2 genetic polymorphisms with ischaemic stroke.ResultsThe results obtained demonstrate that the activities of collectin-bound MASP-1 and MASP-2 in patients with ischaemic stroke are significantly higher than those in healthy subjects (p<0.001). According to the data obtained for genotyping, the rs3203210 polymorphism in the MASP1 gene and the rs147270785 polymorphism in the MASP2 gene are associated with ischaemic stroke (p<0.0001).ConclusionsIn conclusion we suggest that the complement lectin pathway serine proteases, MASP-1 and MASP-2, can be associated with ischaemic stroke development risk and may participate in pathological events leading to post-ischaemic brain damage. Moreover rs3203210 and rs147270785 single nucleotide polymorphisms in the MASP1 and MASP2 genes, respectively, are strongly associated with ischaemic stroke, and the minor rs3203210*C and rs147270785*A alleles of these polymorphisms may be considered as protective factors for ischameic stroke, at least in the Armenian population.

show abstract

“…At the same time, it has been shown to have a strong signal of balancing selection in African primate populations (Tung et al 2009). Likewise, MASP2 has been associated with immune response to several diseases, including Chagas disease (Boldt et al 2011), hepatitis C (Tulio et al 2011), and placental malaria (Holmberg et al 2012). Mutations in this gene (including rs12711521 (Boldt et al 2011), see Table S3) have been linked to both the activity (Thiel et al 2009) and expression levels (Thiel et al 2007) of the protein.…”

Section: Application To Human Populationsmentioning

confidence: 99%

Learning Natural Selection from the Site Frequency Spectrum

et al. 2013

View full text Add to dashboard Cite

Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Many tests have been proposed to identify the genomic signatures of natural selection by quantifying the skew in the site frequency spectrum (SFS) under selection relative to neutrality. We build upon recent work that connects many of these tests under a common framework, by describing how selective sweeps affect the scaled SFS. We show that the specific skew depends on many attributes of the sweep, including the selection coefficient and the time under selection. Using supervised learning on extensive simulated data, we characterize the features of the scaled SFS that best separate different types of selective sweeps from neutrality. We develop a test, SFselect, that consistently outperforms many existing tests over a wide range of selective sweeps. We apply SFselect to polymorphism data from a laboratory evolution experiment of Drosophila melanogaster adapted to hypoxia and identify loci that strengthen the role of the Notch pathway in hypoxia tolerance, but were missed by previous approaches. We further apply our test to human data and identify regions that are in agreement with earlier studies, as well as many novel regions. N ATURAL selection works by preferentially favoring carriers of beneficial (fit) alleles. At the genetic level, the increased fitness may stem from two sources: either a de novo mutation that is beneficial in the current environment or new environmental stress leading to increased relative fitness of an existing allele. Over time, haplotypes carrying such variants start to dominate the population, causing reduced genetic diversity. This process, known as a selective sweep, is mitigated by recombination and can therefore be observed mostly in the vicinity of the beneficial allele. Improving our ability to detect the genomic signatures of selection is crucial for shedding light on genes responsible for adaptation to environmental stress, including disease.Many tests of neutrality have been proposed based on the site frequency spectrum (Tajima 1989;Fay and Wu 2000;Zeng et al. 2006;Chen et al. 2010;Udpa et al. 2011). We start by describing these tests in a common framework delineated by Achaz (2009). The data, namely genetic variants from a population sample, is typically represented as a matrix with m columns corresponding to segregating sites, and n rows corresponding to individual chromosomes. The sample is chosen from a much larger population of N diploid individuals, where chromosomes are connected by a (hidden) genealogy and mutations occurring in a certain lineage are inherited by all of its descendants ( Figure 1A). Thus, in the example shown in Figure 1A, the mutation at locus 4 appears in four chromosomes from the sample, or 0.5 frequency. Following Fu (1995), let j i denote the number of polymorphic sites at frequency i/n in a sample of size n. The site frequency spectrum (SFS) ...

show abstract

MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection

Cited by 33 publications

References 27 publications

Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke

Learning Natural Selection from the Site Frequency Spectrum

Contact Info

Product

Resources

About