Immunogenetic Control of Antibody Responsiveness in a Malaria Endemic Area

Carpenter, Danielle; Abushama, Hind Mohamed; Bereczky, Sándor; Färnert, Anna; Rooth, Ingegerd; Quinnell, Rupert J.; Shaw, Marie‐Anne

doi:10.1016/j.humimm.2006.12.002

Cited by 24 publications

(23 citation statements)

References 20 publications

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“…In line with the known role of IL-13 in induction of Th2 responses, rs20541polymorphisms have also been linked to allergy and autoimmune disease [52], [53] as well as altered outcomes of helminth (Schistosome spp) infections [54]. Our data support other studies implicating IL-13 polymorphisms with risk of severe malaria in Thai adults [55], [56] and associations between 5q31–q33 haplotypes (which span the IL13 locus) and antimalarial antibody responses [57]; the recurrent link between IL-13 and risk of severe malaria would seem to warrant further investigation.…”

Section: Discussionsupporting

confidence: 89%

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

et al. 2012

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Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP's, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 1–10 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1α gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS, G6PD). It identifies two X-linked genes associated with altered risk of severe malaria in females, identifies mutations in ADCY9, IL1A and CD40L as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels, and also identifies novel genetic associations with severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are required to test the generality of these associations and to understand their functional consequences.

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Section: Discussionsupporting

confidence: 89%

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

et al. 2012

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“…Therefore, unique functional polymorphisms in the promoter and/or coding region(s) of cytokine genes [8,10] may be critical in the development and clinical course of malaria. Indeed, polymorphisms in genes encoding IL10, IL4 and TNFA [11,12] have been associated with susceptibility to disease. However, the functional role of TNF-promoter polymorphisms that are associated with severe malaria [13-15] still remains open to question [11,15,16] especially as the surrounding MHC class III region has many other interesting immunological genes and complex patterns of linkage disequilibrium [17].…”

Section: Introductionmentioning

confidence: 99%

Association of Cytokine and Toll-Like Receptor Gene Polymorphisms with Severe Malaria in Three Regions of Cameroon

et al. 2013

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P. falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical human genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity that would be invaluable for vaccine development. We investigated the effect of single nucleotide polymorphisms (SNPs) on malaria pathology in a case- control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Twenty nine polymorphisms in cytokine and toll-like receptor (TLR) genes as well as the sickle cell trait (HbS) were assayed on the Sequenom iPLEX platform. Our results confirm the known protective effect of HbS against severe malaria and also reveal a protective effect of SNPs in interleukin-10 (IL10) cerebral malaria and hyperpyrexia. Furthermore, IL17RE rs708567 GA and hHbS rs334 AT individuals were associated with protection from uncomplicated malaria and anaemia respectively in this study. Meanwhile, individuals with the hHbS rs334 TT, IL10 rs3024500 AA, and IL17RD rs6780995 GA genotypes were more susceptible to severe malarial anaemia, cerebral malaria, and hyperpyrexia respectively. Taken together, our results suggest that polymorphisms in some immune response genes may have important implications for the susceptibility to severe malaria in Cameroonians. Moreover using uncomplicated malaria may allow us to identify novel pathways in the early development of the disease.

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“…The IL10 gene has more than 27 polymorphic sites associated with SNPs that result in the differential production and expression of the cytokine [17, 36, 79], autoimmune and inflammatory diseases [80], bacterial [81] and viral infections [75], and human malaria [21]. The allele distributions for T (-819) and A (-592) in our results were 35.4% and 31.2%, respectively; these distributions were higher in Europeans than in Africans but lacked significant associations.…”

Section: Discussionmentioning

confidence: 99%

Frequency ofTNFA,INFG, andIL10Gene Polymorphisms and Their Association with MalariaVivaxand Genomic Ancestry

Furini

Cassiano

Capobianco

et al. 2016

Mediators of Inflammation

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Polymorphisms in cytokine genes can alter the production of these proteins and consequently affect the immune response. The trihybrid heterogeneity of the Brazilian population is characterized as a condition for the use of ancestry informative markers. The objective of this study was to evaluate the frequency of -1031T>C, -308G>A and -238G>A TNFA, +874 A>T IFNG and -819C>T, and -592C>A IL10 gene polymorphisms and their association with malaria vivax and genomic ancestry. Samples from 90 vivax malaria-infected individuals and 51 noninfected individuals from northern Brazil were evaluated. Genotyping was carried out by using ASO-PCR or PCR/RFLP. The genomic ancestry of the individuals was classified using 48 insertion/deletion polymorphism biallelic markers. There were no differences in the proportions of African, European, and Native American ancestry between men and women. No significant association was observed for the allele and genotype frequencies of the 6 SNPs between malaria-infected and noninfected individuals. However, there was a trend toward decreasing the frequency of individuals carrying the TNF-308A allele with the increasing proportion of European ancestry. No ethnic-specific SNPs were identified, and there was no allelic or genotype association with susceptibility or resistance to vivax malaria. Understanding the genomic mechanisms by which ancestry influences this association is critical and requires further study.

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Immunogenetic Control of Antibody Responsiveness in a Malaria Endemic Area

Cited by 24 publications

References 20 publications

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

Association of Cytokine and Toll-Like Receptor Gene Polymorphisms with Severe Malaria in Three Regions of Cameroon

Frequency ofTNFA,INFG, andIL10Gene Polymorphisms and Their Association with MalariaVivaxand Genomic Ancestry

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