Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India

In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under age 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1–4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11–0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06–0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

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Faculty Opinions recommendation of The role of mannose-binding lectin in susceptibility to infection in preterm neonates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1104387.560408 ◽

2008 ◽

Author(s):

Steven Witkin

Keyword(s):

Mannose Binding Lectin ◽

Preterm Neonates ◽

Susceptibility To Infection ◽

Mannose Binding ◽

Binding Lectin

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THE ASSOCIATION BETWEEN GENETIC POLYMORPHISMS OF TOLL-LIKE RECEPTORS AND MANNOSE-BINDING LECTIN AND ACTIVE TUBERCULOSIS IN HIV-INFECTED PATIENTS

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2019-11-4-61-69 ◽

2020 ◽

Vol 11 (4) ◽

pp. 61-69

Author(s):

E. I. Kulabukhova ◽

K. O. Mironov ◽

E. A. Dunaeva ◽

D. E. Kireev ◽

A. N. Narkevich ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Active Tuberculosis ◽

Mannose Binding Lectin ◽

Toll Like Receptors ◽

Mannose Binding ◽

Binding Lectin

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A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

Diagnostics ◽

10.3390/diagnostics11020301 ◽

2021 ◽

Vol 11 (2) ◽

pp. 301

Author(s):

Jana Mrazkova ◽

Petr Sistek ◽

Jan Lochman ◽

Lydie Izakovicova Holla ◽

Zdenek Danek ◽

...

Keyword(s):

Association Studies ◽

Genetic Association Studies ◽

Cost Effective ◽

European Population ◽

Mannose Binding Lectin ◽

Nucleotide Polymorphisms ◽

Online Application ◽

Czech Population ◽

Mannose Binding ◽

Binding Lectin

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.

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Mannose-binding lectin genetics: from A to Z

Biochemical Society Transactions ◽

10.1042/bst0361461 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1461-1466 ◽

Cited By ~ 75

Author(s):

Peter Garred

Keyword(s):

Epidemiological Studies ◽

Mannose Binding Lectin ◽

Host Cells ◽

Lectin Pathway ◽

Mannose Binding ◽

The Stability ◽

Genetically Determined ◽

Micro Organisms ◽

Binding Lectin

MBL (mannose-binding lectin) is primarily a liver-derived collagen-like serum protein. It binds sugar structures on micro-organisms and on dying host cells and is one of the four known mediators that initiate activation of the complement system via the lectin pathway. Common variant alleles situated both in promoter and structural regions of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variations in MBL serum concentrations influence the susceptibility to and the course of different types of infectious, autoimmune, neoplastic, metabolic and cardiovascular diseases, but this is still a subject under discussion. The fact that these genetic variations are very frequent, indicates a dual role of MBL. This overview summarizes the current molecular understanding of human MBL2 genetics.

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ON VASCULAR STENOSIS, RESTENOSIS AND MANNOSE BINDING LECTIN

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-6720201600010015 ◽

2016 ◽

Vol 29 (1) ◽

pp. 57-59 ◽

Cited By ~ 1

Author(s):

Barbara Stadler KAHLOW ◽

Rodrigo Araldi NERY ◽

Thelma L SKARE ◽

Carmen Australia Paredes Marcondes RIBAS ◽

Gabriela Piovezani Ramos ◽

...

Keyword(s):

Innate Immunity ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

Vascular Stenosis ◽

Micro Organisms ◽

The Complement System ◽

Binding Lectin

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

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