Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria
Izumi Naka,Nao Nishida,Jintana Patarapotikul,Pornlada Nuchnoi,Katsushi Tokunaga,Hathairad Hananantachai,Naoyuki Tsuchiya,Jun Ohashi +7 more
TLDR
A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.Abstract:
It has been previously demonstrated that a single nucleotide polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria. A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients). Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73), showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes. A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.read more
Citations
More filters
Journal ArticleDOI
The host genetic diversity in malaria infection
Vitor R. R. Mendonça,Vitor R. R. Mendonça,Marilda Souza Goncalves,Marilda Souza Goncalves,Manoel Barral-Netto,Manoel Barral-Netto +5 more
TL;DR: The genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome are reviewed and polymorphisms in genes related to molecules involved in mechanisms of cytoadherence are discussed.
Journal ArticleDOI
Candidate human genetic polymorphisms and severe malaria in a Tanzanian population.
Alphaxard Manjurano,Taane G. Clark,Behzad Nadjm,George Mtove,Hannah Wangai,Nuno Sepúlveda,Susana Campino,C. A. Maxwell,Raimos Olomi,K Rockett,Anna E. Jeffreys,Eleanor M. Riley,Hugh Reyburn,Chris Drakeley +13 more
TL;DR: Previously known genetic associations with protection from severe malaria (HbS, G6PD) are confirmed and mutations in ADCY9, IL1A and CD40L are identified as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels.
Journal ArticleDOI
Neuregulin-1 attenuates mortality associated with experimental cerebral malaria
Wesley Solomon,Nana O. Wilson,Leonard M. Anderson,Sidney Pitts,John Patrickson,Mingli Liu,Byron D. Ford,Jonathan K. Stiles +7 more
TL;DR: This study suggests that NRG-1 attenuates ECM-associated brain inflammation and injuries and may represent a novel supportive therapy for the management of CM.
Journal ArticleDOI
Genetic polymorphisms associated with anti-malarial antibody levels in a low and unstable malaria transmission area in southern Sri Lanka
Rajika L. Dewasurendra,Prapat Suriyaphol,Sumadhya Deepika Fernando,Richard Carter,Kirk A. Rockett,Patrick H. Corran,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Nadira D. Karunaweera,Nadira D. Karunaweera +9 more
TL;DR: Evidence is suggestive of an age–acquired immunity in this study population in spite of low malaria transmission levels, suggesting that these host genetic mutations might have an individual or collective effect on inducing or/and maintaining high anti-malarial antibody levels.
Journal ArticleDOI
A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13
Audrey Brisebarre,Audrey Brisebarre,Brice Kumulungui,S Sawadogo,Alexandre Atkinson,Alexandre Atkinson,Séverine Garnier,Séverine Garnier,Francis Fumoux,Pascal Rihet,Pascal Rihet +10 more
TL;DR: A new genome-wide significant malaria locu on chromosome 17p12 and a new suggestive locus on chromosome 19p13 are reported, which are believed to be significant as loci controlling mild malaria or asymptomatic parasitaemia.
References
More filters
Journal ArticleDOI
Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33
Sandrine Marquet,Laurent Abel,Dominique Hillaire,Hélia Dessein,Jorge Kalil,Josué Feingold,Jean Weissenbach,Alain Dessein +7 more
TL;DR: To localize this gene, referred to as SM1, a genome-wide study on 142 Brazilian subjects belonging to 11 informative families showed a linkage to only one region, on chromosome 5q31–q33, with maximum two-point lod scores, indicating a close proximity to CSF1R as the most likely location of SM1.
Journal ArticleDOI
An IL-13 promoter polymorphism associated with increased risk of allergic asthma.
van der Pouw Kraan Tc,van Veen A,L. C. M. Boeije,van Tuyl Sa,de Groot Er,S O Stapel,A.H.F. Bakker,Cornelis L. Verweij,Lucien A. Aarden,van der Zee Js +9 more
TL;DR: The identification of a novel IL-13 promoter polymorphism (C to T exchange) at position −1055 is described, and it is postulate that the presence of this polymorphism predisposes to the development of allergic asthma.
Journal ArticleDOI
The MRN complex: coordinating and mediating the response to broken chromosomes
TL;DR: A model for how DSBs are sensed and the cellular responses to them are mediated is proposed and suggests that MRN could function as a lesion‐specific sensor.
Journal ArticleDOI
Regulation of the Th2 cytokine locus by a locus control region.
TL;DR: Investigation of the global locus-specific regulation of these genes using BAC transgenic mice containing the murine Th2 cytokine cluster carrying an IL4 promoter-luciferase reporter suggested the presence of an LCR in the locus.
Journal ArticleDOI
Chromatin Structure and Gene Regulation in the Immune System
TL;DR: The interleukin-4 gene serves as a primary model for exploring the events involved in the acquisition and heritable maintenance of a decondensed chromatin structure and the mechanisms by which the remodeling of specific nucleosomes in the vicinity of a promoter can contribute to rapid activation following cell stimulation.