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Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans
R Bellamy1, C Ruwende, K P McAdam
1Wellcome Trust Centre for Human Genetics, Oxford University, UK.
Insights
Major malaria, tuberculosis (TB), and hepatitis B virus (HBV) genotypes were studied in The Gambia. MBP variants were not linked to increased risk for these diseases, though one mutation showed weak TB resistance.
Area of Science:
- Genetics and Infectious Diseases
- Molecular Biology
- Epidemiology
Background:
- The complement system plays a crucial role in host defense against pathogens.
- The mannose-binding lectin (MBL) protein (MBP) is a key initiator of the lectin pathway of complement activation.
- Genetic variations in the MBL gene (MBP) can lead to altered MBL levels and function, potentially impacting susceptibility to infections.
Purpose of the Study:
- To investigate the association between MBP genotypes and susceptibility to severe malaria, persistent hepatitis B virus (HBV) carriage, and pulmonary tuberculosis (TB) in The Gambia.
- To determine if MBP deficiency is a risk factor for these infectious diseases in a West African population.
Main Methods:
- Retrospective study of MBP genotypes in patients with malaria, TB, and HBV carriage, and healthy controls in The Gambia.
- Genotyping using sequence-specific oligonucleotide analysis to identify MBP variant alleles.
- Comparison of MBP genotype frequencies between disease cases (cerebral malaria, severe malarial anemia, smear-positive pulmonary TB) and controls (mild malaria, healthy blood donors).
Main Results:
- Overall, 46% of individuals were homozygous for the wild-type MBP allele, 45% carried one variant allele, and 8.6% had two variant alleles.
- No significant association was found between MBP variant alleles (homozygous or heterozygous) and increased risk of clinical malaria, persistent HBV carriage, or TB.
- The codon 57 variant allele, common in Africans, showed a weak association with resistance to TB (p = 0.037).
Conclusions:
- MBP deficiency is not a significant risk factor for persistent HBV infection, severe malaria, or pulmonary TB in West Africa.
- While MBP variants do not generally increase susceptibility, a specific variant may offer a degree of protection against TB.
- Further research is needed to fully elucidate the role of MBP in infectious disease susceptibility in diverse populations.
Abstract:
We retrospectively studied MBP genotypes in patients with malaria, tuberculosis (TB), and persistent hepatitis B virus (HBV) carriage, in clinics and hospitals in The Gambia. Children under 10 years with cerebral malaria and/or severe malarial anaemia, were compared with children with symptomatic, mild malaria, and controls of the same age and ethnicity. Adult TB cases with smear-positive pulmonary TB were compared with healthy blood donors from the same ethnic groups. Malaria cases and controls were tested for hepatitis B core antibody (anti-HBc) and surface antigen (HBsAg). TB patients were tested for HIV antibodies. Genotyping used sequence-specific oligonucleotide analysis to identify MBP variant alleles. Overall, 46% (944/2041) of patients and controls were homozygous for the wild-type MBP allele, 45% (922/2041) were carriers of a single variant allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor heterozygotes for MBP variants were at increased risk of clinical malaria, persistent HBV carriage or TB. The most common mutation in Africans, the codon 57 variant allele, was weakly associated with resistance to TB (221/794 in TB cases and 276/844 in controls, p = 0.037). MBP deficiency is not a significant risk factor for persistent HBV, severe malaria nor pulmonary TB in West Africa.