Abstract
BackgroundHBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG) antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies.MethodsIn this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels.ResultsAfter applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i) haemoglobin C with IgG levels; ii) the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii) TNF-863 with IgG3 levels; iv) TNF-857 with IgG levels; and, v) TNF1304 with IgG3, IgG4, and IgG levels.ConclusionTaken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.
Highlights
HBB, Interleukin 4 (IL4), IL12, Tumor necrosis factor (TNF), Lymphotoxin α (LTA), Natural cytotoxicity receptor 3 (NCR3) and Fc-gamma Receptor IIA (FCGR2A) polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG) antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite
Allele frequencies for all single-nucleotide polymorphisms (SNPs) and previously reported family-based associations with parasitaemia and mild malaria are shown in Table 2 and Additional file 1, respectively
haemoglobin C (HbC), LTA + 80, TNF-1031, TNF-238, TNF1304, and NCR3-412 were associated with parasitaemia or mild malaria in this sub-population (Additional file 1)
Summary
HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG) antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. High levels of non-cytophilic IgG4 antibodies have been associated with susceptibility to malaria [14] In this context, several investigators have provided evidence of the genetic control of IgG levels. These include HBB, IL4, TNF, and FCGR2A, which have been associated with both malaria resistance and IgG levels [1,20,21,22,23,24,25] This suggests that those genes control the production of cytophilic IgG subclasses. The objective of this study was to determine the influence of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the IgG subclass patterns of antibodies against P. falciparum antigens in the same population by using a family-based approach
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