Association analyses of NCR3 polymorphisms with P-falciparum mild malaria

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France
Microbes and Infection (Impact Factor: 2.86). 03/2007; 9(2):160-6. DOI: 10.1016/j.micinf.2006.11.002
Source: PubMed


Plasmodium falciparum malaria is a major cause of morbidity and mortality in many developing countries especially in sub-Saharan Africa. A susceptibility locus for mild malaria has been mapped to the MHC region, and TNF polymorphisms have been associated with mild malaria. The Natural Cytotoxicity-triggering Receptor 3 (NCR3) gene is located in the peak region of linkage, and is 15kb distal to TNF. In this study, we considered NCR3 as a candidate gene, and we genotyped ten NCR3 single nucleotide polymorphisms (SNPs). Here, we report evidence of an association between mild malaria and NCR3 -412G>C polymorphism located within the promoter. Population-based association analysis showed that NCR3 -412C carriers had more frequent mild malaria attacks than NCR3 -412GG individuals (P=0.001). Using the family-based association test (FBAT) program and its phenotype (PBAT) option, we further found that NCR3 -412C (P=0.0009) and a haplotype containing NCR3 -412C (P=0.008) were significantly associated with increased risk of mild malaria, and that the association was not due to the association of TNF with mild malaria. These observations suggest that there are at least two genes located on the central region of MHC involved in genetic control of human malaria. The association of NCR3 with malaria should provide new insights into the role of Natural Killer cells in this common disease.

Download full-text


Available from: Mathieu Barbier, Sep 16, 2015
  • Source
    • "Samples were first subject to prior whole-genome amplification by primer extension pre-amplification [28]. For IL4, FCGR2A, NCR3, TNF, LTA, and IL12B polymorphisms, the data sets previously reported were used [6,9,10,29,30]. Briefly, genotypes for NCR3, TNF, LTA, and IL12B polymorphisms have been obtained by sequencing with a CEQ 8000 automated fluorescent sequencer (Beckman Coulter, Roissy CDG, France), whereas FCGR2A H/R131 genotypes was determined by using PCR and allele-specific restriction enzyme digestion methods as previously described [31]. The call rate was higher than 88% for all the polymorphisms, based on the 193 individuals, for which the IgG subclass levels have been measured; the median call rate was 94%. "
    [Show abstract] [Hide abstract]
    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. Conclusion 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.
    Full-text · Article · Sep 2012 · Malaria Journal
  • Source
    • "The identification of genes underlying complex diseases remains a challenging task, and few genes have been identified. Nevertheless, IL13 (chromosome 5q31-q33), TNF and NCR3 (chromosome 6p21-p23), PARK2 and PACRG (chromosome 6q25) polymorphisms have been associated with schistosomiasis (36), mild malaria (37,38), and leprosy (39), respectively. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.
    Full-text · Article · Oct 2011 · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.]
  • Source
    • "GRPs have been and will continue to be an important basis for understanding infectious diseases in humans. A very good example for translational research was presented by Pascal Rihet, who identified genomic susceptibility regions to malaria in human populations in Africa (Delahaye et al. 2007) and then continued to compare these results with studies in mouse GRPs. In this way, a region on human chromosome 5 and its homologous regions on mouse chromosomes 11 and 18 were identified. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The first scientific meeting of the newly established European SYSGENET network took place at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, April 7-9, 2010. About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. In addition, the future of GRP resources and phenotyping in Europe was discussed.
    Full-text · Article · Aug 2010 · Mammalian Genome
Show more