Multiplex sequence-specific polymerase chain reaction reveals new MASP2 haplotypes associated with MASP-2 and MAp19 serum levels

Boldt, Angelica Beate Winter; Grisbach, Caroline; Steffensen, Rudi; Thiel, Steffen; Kun, Jürgen F. J.; Jensenius, Jens Christian; Messias-Reason, Iara

doi:10.1016/j.humimm.2011.05.015

Cited by 23 publications

(42 citation statements)

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“…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

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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.

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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

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“…We optimized a multiplex sequence-specific amplification method (multiplex PCR-SSP) to rapidly identify nine single nucleotide polymorphisms (SNPs rs61735600, rs7548659, rs72550870, rs56392418, rs17409276, rs12711521, rs2273346, rs12085877 and rs1782455) and ten corresponding haplotypes (*1A, *1B1-h, *1B2-h, *1C1-l, *1C2-l, *2A1, *2A2-l, *2B1-i, *2B2A-i, *2B2B-l ) at low cost and with high accuracy, as previously published [12]. We further investigated the SNPs rs2273344 and rs9430347 flanking the alternative exon 5.…”

Section: Methodsmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) located in the exons for the CUB1, EGF and serine protease domain have been shown to modify MASP-2 functions [8]–[11]. Other polymorphisms occurring in intron 9 and in exon 10 (encoding the last CCP) were associated with different MASP-2 and MAp19 levels [9], [12], [13] (Figure 1). Based on these SNPs, we recently described and named ten haplotypes according to their phylogenetic relationships [12].…”

Section: Introductionmentioning

confidence: 99%

“…Other polymorphisms occurring in intron 9 and in exon 10 (encoding the last CCP) were associated with different MASP-2 and MAp19 levels [9], [12], [13] (Figure 1). Based on these SNPs, we recently described and named ten haplotypes according to their phylogenetic relationships [12]. Five haplotypes share g.24762C in exon 12 and belong to clade 1: *1A (most ancient), *1B1-h and *1B2-h (both associated with higher MASP-2 levels) and *1C1-l and *1C2-l (who share the p.126L amino acid and are associated with low MASP-2 levels – additionally, *1C2-l bears the deficiency-causing p.439H variant).…”

Section: Introductionmentioning

confidence: 99%

“…Arrows pointing downward: SNPs reportedly associated with low MASP-2 levels (400–200 ng/mL) or very low MASP-2 levels (under 200 ng/mL, shown as a double arrow) [9], [10], [12]. Arrows pointing upward: SNPs reportedly associated with high MASP-2 levels (above 600 ng/mL) [12]. SNPs with unknown or neutral effect are indicated without an arrow.…”

Section: Introductionmentioning

confidence: 99%

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Leprosy Association with Low MASP-2 Levels Generated by MASP2 Haplotypes and Polymorphisms Flanking MAp19 Exon 5

Boldt

Goeldner

Stahlke³

et al. 2013

PLoS ONE

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BackgroundThe gene MASP2 (mannan-binding lectin (MBL)-associated serine protease 2) encodes two proteins, MASP-2 and MAp19 (MBL-associated protein of 19 kDa), bound in plasma to MBL and ficolins. The binding of MBL/MASP-2 and ficolin/MASP-2 complexes to microorganisms activates the lectin pathway of complement and may increase the ingestion of intracellular pathogens such as Mycobacterium leprae.MethodsWe haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 219 Brazilian leprosy patients (131 lepromatous, 29 borderline, 21 tuberculoid, 14 undetermined, 24 unspecified), 405 healthy Brazilians and 291 Danish blood donors with previously determined MASP-2 and MAp19 levels. We also evaluated MASP-2 levels in further 46 leprosy patients and 69 Brazilian controls.ResultsTwo polymorphisms flanking exon 5 of MASP2 were associated with a dominant effect on high MASP-2 levels and an additive effect on low MAp19 levels. Patients presented lower MASP-2 levels (P = 0.0012) than controls. The frequency of the p.126L variant, associated with low MASP-2 levels (below 200 ng/mL), was higher in the patients (P = 0.0002, OR = 4.92), as was the frequency of genotypes with p.126L (P = 0.00006, OR = 5.96). The *1C2-l [AG] haplotype, which harbors p.126L and the deficiency-causing p.439H variant, has a dominant effect on the susceptibility to the disease (P = 0.007, OR = 4.15). Genotypes composed of the *2B1-i and/or *2B2A-i haplotypes, both associated with intermediate MASP-2 levels (200–600 ng/mL), were found to be protective against the disease (P = 0.0014, OR = 0.6). Low MASP-2 levels (P = 0.022), as well as corresponding genotypes with *1C2-l and/or *2A2-l but without *1B1-h or *1B2-h, were more frequent in the lepromatous than in other patients (P = 0.008, OR = 8.8).ConclusionsIn contrast with MBL, low MASP-2 levels increase the susceptibility to leprosy in general and to lepromatous leprosy in particular. MASP2 genotypes and MASP-2 levels might thus be of prognostic value for leprosy progression.

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MASP1 and MASP2

Boldt¹,

Boschmann²,

Catarino³

et al. 2016

Encyclopedia of Signaling Molecules

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Multiplex sequence-specific polymerase chain reaction reveals new MASP2 haplotypes associated with MASP-2 and MAp19 serum levels

Cited by 23 publications

References 54 publications

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

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

Leprosy Association with Low MASP-2 Levels Generated by MASP2 Haplotypes and Polymorphisms Flanking MAp19 Exon 5

MASP1 and MASP2

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