Dataset Information

Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5.

ABSTRACT:

Background

The 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.

Methods

We 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.

Results

Two 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).

Conclusions

In 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.

SUBMITTER: Boldt AB

PROVIDER: S-EPMC3728295 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5.

Boldt Angelica Beate Winter AB Goeldner Isabela I Stahlke Ewalda R S ER Thiel Steffen S Jensenius Jens Christian JC de Messias-Reason Iara José Taborda IJ

PloS one 20130730 7

<h4>Background</h4>The 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.<h4>Methods</h4>We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in ...[more]

PMID: 23935922

Similar Datasets

Project description:Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectious diseases, including leprosy. Host immune response has a major impact on the clinical manifestation of leprosy since only a few individuals infected with Mycobacterium leprae will develop the disease. Therefore, the aim of this study was to evaluate the influence of MBL2 exon 1 polymorphisms (rs5030737, rs1800450, and rs1800451) on the MBL levels and leprosy immunopathogenesis. This case-control study included 350 leprosy patients from Southern Brazil, with 279 classified as multibacillary (MB) and 71 as paucibacillary (PB). The control group consisted of 350 non-consanguineous individuals, who were not diagnosed with leprosy or other infectious and autoimmune diseases. Genotyping was performed by PCR-sequence specific primers, and the MBL serum concentrations were evaluated by ELISA. MBL2 exon 1 polymorphisms were analyzed individually and grouped as genotypes, considering "A" as the wild allele and "O" as the presence of at least one polymorphism (D, B, or C variants). Differences were not observed in the distribution of genotypic and allelic frequencies between leprosy per se patients and controls. However, in a haplotypic analysis, the TGG haplotype presented a risk for development of leprosy per se in women when compared to the wild haplotype (CGG) (OR = 2.69). Comparing patients with MB and PB, in a multivariate analysis, the B variant was associated with the susceptibility of developing the MB form of leprosy (OR = 2.55). Besides that, the CAG haplotype showed an increased susceptibility to develop MB leprosy in women compared to men. It was observed that the A/O genotype in women was associated with a susceptibility to leprosy development per se (OR = 1.66) and progression to MB leprosy (OR = 3.13). In addition, the MBL serum concentrations were in accordance with the genotyping analysis. In summary, our data suggest that MBL2 exon 1 polymorphisms are associated with an increased risk to leprosy development and progression.

Dataset Information

Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5.

Background

Methods

Results

Conclusions

Publications

Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5.

Similar Datasets

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