Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali

Vafa, Manijeh; Maiga, Bakary; Israelsson, Elisabeth; Dolo, Amagana; Doumbo, Ogobara K.

doi:10.1016/j.micinf.2009.04.017

Cited by 20 publications

(20 citation statements)

References 27 publications

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“…In a study performed in the same ethnic groups and region, the IL4-590 (T vs. C alleles) was associated with higher parasite prevalence in Fulani (compared to Dogon). Our data are also consistent with the reported high correlation between the IL4 polymorphism and IgE production in asymptomatic individuals belonging to the Fulani groups [32,33]. …”

Section: Discussionsupporting

confidence: 93%

Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali

et al. 2013

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Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10-15). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.

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Section: Discussionsupporting

confidence: 93%

Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali

et al. 2013

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“…For example, several genes in the chromosome region 5q31–q33 region are likely to regulate antibody responses to blood stage malaria infection [43]–[45], including a single nucleotide polymorphism (SNP) at the transcriptional start site of the IL-4 gene promoter region ( -590C/T ), considered to influence the transcriptional levels of IL-4 [46]. Studies in Burkina Faso and Ghana indicate that the IL-4 -590T allele is associated with higher levels of IgE among severe malaria patients [47], [48], and a study in Mali shows the same allele to be associated with higher levels of P. falciparum specific IgE reactivity in the Fulani population, although not in another ethnic group [49]. Surveys in Mali, Gabon and Sudan indicate that variation in plasma IgG2 levels to malaria antigens is non-randomly associated with the amino acid 131 polymorphism of its receptor FcγRIIa that affects binding [50]–[52].…”

Section: Discussionmentioning

confidence: 99%

Heritability of Antibody Isotype and Subclass Responses to Plasmodium falciparum Antigens

et al. 2009

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BackgroundIt is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters.Methodology/Principal FindingsThis study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) naturally acquired to P. falciparum blood stage antigens AMA1, MSP1-19, MSP2 (two allelic types) and MSP3 (two allelic types). Separate analyses were performed on plasma from 213 pairs of Gambian adult twins, 199 child twin pairs sampled in a dry season when there was little malaria transmission, and another set of 107 child twin pairs sampled at the end of the annual wet season when malaria was common. There were significantly positive heritability (h 2) estimates for 48% (20/42) of the specific antibody assays (for the seven isotypes and subclasses to the six antigens tested) among the adults, 48% (20/42) among the children in the dry season and 31% (13/42) among the children in the wet season. In children, there were significant heritability estimates for IgG4 reactivity against each of the antigens, and this subclass had higher heritability than the other subclasses and isotypes. In adults, 75% (15/20) of the significantly heritable antigen-specific isotype responses were attributable to non-HLA class II genetic variation, whereas none showed a significant HLA contribution.SignificanceGenome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.

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“…Moreover, the same study reported an association between the IL-4-590 T allele and the prevalence of P. falciparum infection within the Fulani but not in the Dogon (Vafa et al, 2007). Interestingly within the Fulani, the T allele was associated with increased levels of total and anti-malarial IgE, suggesting that the impact of IL-4-590 variants on antibody levels may vary in different ethnic populations, and that might affect the immunoglobulin-class and subclass distributions (Vafa et al, 2009b). The association between this polymorphism and elevated serum antibody levels in the Fulani would suggest the selection of a protective haplotype, while the lack of association in Mossi indicates that this polymorphism is not functional or might be in linkage disequilibrium with others protective genes .…”

Section: Human Genetic Variations and Sympatric Ethnicity Difference mentioning

confidence: 91%

“…For example, studies have shown that the IL4-590 T allele is present in 75% of the Fulani, twice the frequency compared to their sympatric neighbors, raising the possibility that differences in IL-4 expression and/or function plays a role in protection from malaria (Vafa et al, 2007(Vafa et al, , 2009b. Moreover, the same study reported an association between the IL-4-590 T allele and the prevalence of P. falciparum infection within the Fulani but not in the Dogon (Vafa et al, 2007).…”

Section: Human Genetic Variations and Sympatric Ethnicity Difference mentioning

confidence: 98%

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

et al. 2015

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Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali

Cited by 20 publications

References 27 publications

Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali

Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali

Heritability of Antibody Isotype and Subclass Responses to Plasmodium falciparum Antigens

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

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