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Association of a new mannose-binding lectin variant with severe malaria in Gabonese children
A B W Boldt1, A Luty, M P Grobusch
1Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.
Abstract:
Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P=0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.
Insights
Mannose-binding lectin (MBL2) gene variants influence infection severity. New MBL2 haplotypes were identified, with a novel variant linked to severe malaria susceptibility, suggesting malaria shaped MBL2 evolution.
Area of Science:
- Immunogenetics
- Evolutionary medicine
- Infectious diseases
Background:
- Mannose-binding lectin (MBL2) variants affect protein levels and function, correlating with infection and autoimmune disease severity.
- High frequencies of these MBL2 variants suggest a selective advantage against prevalent diseases.
Purpose of the Study:
- To identify novel MBL2 allelic haplotypes and variants.
- To investigate the association between MBL2 variants and malaria severity.
- To explore the relationship between MBL2 levels, genotypes, and cytokine profiles in malaria patients.
Main Methods:
- Screening of MBL2 in 136 children with uncomplicated malaria, 131 with severe malaria, and 39 healthy schoolchildren.
- Identification of 14 new MBL2 allelic haplotypes, including two with non-synonymous variants.
- Analysis of MBL plasma levels, MBL2 genotypes, and plasma cytokine/chemokine concentrations.
Main Results:
- Discovery of 14 novel MBL2 allelic haplotypes, two featuring non-synonymous variants.
- Significant association found between a novel MBL2 variant and susceptibility to severe malaria (P=0.010).
- Higher MBL plasma levels and corresponding MBL2 genotypes correlated with reduced concentrations of specific cytokines and chemokines in malaria patients.
Conclusions:
- Malaria may have acted as an evolutionary pressure shaping MBL2 polymorphism in African populations.
- The identified MBL2 variant contributes to severe malaria susceptibility.
- MBL2 genotype influences the inflammatory response in malaria.
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