title: Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  After 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.
  
  
  CONCLUSIONS
  Taken 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.
authors.affiliation: UMR1090 TAGC, INSERM, Marseille, F-13288, France.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Afridi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Atkinson
authors.forename: Séverine
authors.initials: S
authors.lastname: Garnier
authors.forename: Francis
authors.initials: F
authors.lastname: Fumoux
authors.forename: Pascal
authors.initials: P
authors.lastname: Rihet
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood* / Q000145:classification; D000953:Antigens, Protozoan; D002050:Burkina Faso; D002648:Child; D002675:Child, Preschool; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000145:classification; D007223:Infant; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D017572:Leukotriene A4 / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D018512:Parasitemia / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C445323:FCGR2A protein, human; D006454:Hemoglobins; C508598:IL4 protein, human; D007074:Immunoglobulin G; D017572:Leukotriene A4; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; C020622:hemoglobin B