Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India
| Autor: | Gagandeep Kang, Prasanna S. Premkumar, Sitara Swarna Rao Ajjampur, Savitha Varatharajan, Farzana Begum Liakath, Chanduni Syed, Honorine D. Ward |
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| Rok vydání: | 2021 |
| Předmět: |
Diarrhea
TIRAP Urban Population Cryptosporidiosis India Single-nucleotide polymorphism Adaptive Immunity Mannose-Binding Lectin Asymptomatic Cohort Studies Poverty Areas Virology Genotype Humans Medicine Poverty Subclinical infection Mannan-binding lectin Polymorphism Genetic business.industry Toll-Like Receptors Infant Articles Immunity Innate TLR2 Infectious Diseases Case-Control Studies Child Preschool Immunology Parasitology medicine.symptom business |
| Zdroj: | The American Journal of Tropical Medicine and Hygiene |
| ISSN: | 1476-1645 0002-9637 |
| DOI: | 10.4269/ajtmh.20-0617 |
| Popis: | In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 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. |
| Databáze: | OpenAIRE |
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