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We therefore carried out a family\u2010based (<jats:italic>n<\/jats:italic> = 918 post\u2013quality control fully genotyped and phenotyped individuals) candidate gene study for symptomatic VL or asymptomatic delayed\u2010type 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 (<jats:italic>P<\/jats:italic> = 5.7e\u201004; p<jats:sub>corrected<\/jats:sub> = 0.026) 3.8 kb upstream of <jats:italic>TGFBR2<\/jats:italic>, the gene encoding the type 2 receptor for transforming growth factor beta (TGF\u03b2). A second inhibitory member of the TGB\u03b2 superfamily signaling pathway, <jats:italic>SMAD7<\/jats:italic>, was associated with the DTH phenotype (SNP rs7238442: <jats:italic>P<\/jats:italic> = 0.001; p<jats:sub>corrected<\/jats:sub> = 0.051). The most significant association for the DTH phenotype was with SNP rs10800309 (<jats:italic>P<\/jats:italic> = \u20138.4e\u201006; p<jats:sub>corrected<\/jats:sub> = 3.9e\u201004) situated 3.1 kb upstream of <jats:italic>FCGR2A<\/jats:italic>, the gene encoding the low\u2010affinity IIa receptor for the Fc fragment of IgG. Overall, our results imply a role for IgG\u2010mediated inflammation in determining DTH associated with asymptomatic infection and contribute to growing evidence that the TGF\u03b2 pathway is important in the immunopathogenesis of VL.<\/jats:p>","DOI":"10.1111\/ahg.12180","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T04:02:42Z","timestamp":1483588962000},"page":"41-48","source":"Crossref","is-referenced-by-count":10,"title":["Comprehensive candidate gene analysis for symptomatic or asymptomatic outcomes of <i>Leishmania infantum<\/i> infection in Brazil"],"prefix":"10.1111","volume":"81","author":[{"given":"Jason L.","family":"Weirather","sequence":"first","affiliation":[{"name":"Interdisciplinary Program in Genetics University of Iowa  Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya","family":"Duggal","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana L.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Federal University of Rio Grande do Norte  Natal RN Brazil"},{"name":"Institute of Tropical Medicine of Rio Grande do Norte Federal University of Rio Grande do Norte  Natal RN Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria R.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of Rio Grande do Norte Federal University of Rio Grande do Norte  Natal RN Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniella R.","family":"Martins","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of Rio Grande do Norte Federal University of Rio Grande do Norte  Natal RN Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henio G.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Federal University of Rio Grande do Norte  Natal RN Brazil"},{"name":"Institute of Tropical Medicine of Rio Grande do Norte Federal University of Rio Grande do Norte  Natal RN Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Fakiola","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research University of Cambridge  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenefer M.","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research University of Cambridge  UK"},{"name":"Telethon Kids Institute The University of Western Australia  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selma M. B.","family":"Jeronimo","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of Rio Grande do Norte Federal University of Rio Grande do Norte  Natal RN Brazil"},{"name":"Department of Biochemistry Federal University of Rio Grande do Norte, Natal, RN and the National Institute of Science and Technology of Tropical Diseases  Natal Rio Grande do Norte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Genetics University of Iowa  Iowa City IA USA"},{"name":"Departments of Internal Medicine and Microbiology University of Iowa and the Iowa City Veterans\u2019 Affairs Medical Center  Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng786"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aad0416"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_7_5_1","volume-title":"Immunology of Infectious Diseases","author":"Blackwell J. 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