Comprehensive candidate gene analysis for symptomatic or asymptomatic outcomes ofLeishmania infantuminfection in Brazil

Autor:	Michaela Fakiola, Priya Duggal, Jenefer M. Blackwell, Henio G. Lacerda, Mary E. Wilson, Selma M. B. Jeronimo, Eliana L. Nascimento, Jason L. Weirather, Daniella R. Martins, Gloria R. Monteiro
Rok vydání:	2017
Předmět:	0301 basic medicine Candidate gene biology 030231 tropical medicine Single-nucleotide polymorphism FCGR2A biology.organism_classification medicine.disease Asymptomatic Virology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Visceral leishmaniasis Immunology Genetics medicine SNP medicine.symptom Leishmania infantum Candidate Gene Analysis Genetics (clinical)
Zdroj:	Annals of Human Genetics. 81:41-48
ISSN:	0003-4800
Popis:	Genetic risk factors contribute to asymptomatic versus symptomatic visceral leishmaniasis (VL) outcomes following infection with Leishmania infantum. We therefore carried out a family-based (n = 918 post-quality control fully genotyped and phenotyped individuals) candidate gene study for symptomatic VL or asymptomatic delayed-type hypersensitivity (DTH) skin test phenotypes in highly endemic neighborhoods of northeast Brazil. A total of 248 SNPs were genotyped in 42 genes selected as candidates on the basis of prior genetic, immunological, and transcriptional profiling studies. The most significant association with the VL phenotype was with SNP rs6785358 (P = 5.7e-04; pcorrected = 0.026) 3.8 kb upstream of TGFBR2, the gene encoding the type 2 receptor for transforming growth factor beta (TGFβ). A second inhibitory member of the TGBβ superfamily signaling pathway, SMAD7, was associated with the DTH phenotype (SNP rs7238442: P = 0.001; pcorrected = 0.051). The most significant association for the DTH phenotype was with SNP rs10800309 (P = -8.4e-06; pcorrected = 3.9e-04) situated 3.1 kb upstream of FCGR2A, the gene encoding the low-affinity IIa receptor for the Fc fragment of IgG. Overall, our results imply a role for IgG-mediated inflammation in determining DTH associated with asymptomatic infection and contribute to growing evidence that the TGFβ pathway is important in the immunopathogenesis of VL.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ba9e54a63d37b8cf9237780d53a8a41c https://doi.org/10.1111/ahg.12180 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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