{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:14:07Z","timestamp":1791389647104,"version":"4.3.3"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Leishmaniasis continues to pose a substantial health burden in 97 countries worldwide. The progression and outcome of <jats:italic>Leishmania<\/jats:italic> infection are influenced by various factors, including the cytokine milieu, the skin microbiota at the infection site, the specific <jats:italic>Leishmania<\/jats:italic> species involved, the genetic background of the host, and the parasite load. In endemic regions to leishmaniasis, only a fraction of individuals infected actually develops the disease. Overexpression of IL-13 in naturally resistant C57BL\/6 mice renders them susceptible to <jats:italic>L. major<\/jats:italic> infection. Haplotypes constructed from several single nucleotide variant (SNV) along a chromosome fragment may provide insight into any SNV near the fragment that may be genuinely associated with a phenotype in genetic association studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated nine SNVs (SNV1rs1881457A&amp;gt;C, SNV2rs1295687C&amp;gt;G, SNV3rs2069744C&amp;gt;T, SNV4rs2069747C&amp;gt;T, SNV5rs20541A&amp;gt;G, SNV6rs1295685A&amp;gt;G, SNV7rs848A&amp;gt;C, SNV8rs2069750G &amp;gt;C, and SNV9rs847T&amp;gt;C) spanning the entire <jats:italic>IL13<\/jats:italic> gene in patients with <jats:italic>L. guyanensis<\/jats:italic> cutaneous leishmaniasis (<jats:italic>Lg<\/jats:italic>-CL). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis did not reveal any significant association between the SNVs and susceptibility\/protection against <jats:italic>Lg<\/jats:italic>-CL development. However, haplotype analysis, excluding SNV4rs2069747 and SNV8rs2069750 due to low minor allele frequency, revealed that carriers of the haplotype CCCTAAC had a 93% reduced likelihood developing Lg-CL. Similarly, the haplotypes ACCCGCT (ORadj=0.02 [95% CI 0.00\u20130.07]; <jats:italic>p<\/jats:italic>-value, 6.0\u00d710<jats:sup>\u221219<\/jats:sup>) and AGCTAAC (ORadj=0.00[95% CI 0.00\u20130.00]; <jats:italic>p<\/jats:italic>-value 2.7\u00d710<jats:sup>\u221212<\/jats:sup>) appeared to provide protection against the development of <jats:italic>Lg<\/jats:italic>-CL. Conversely, carriers of haplotype ACCTGCC have 190% increased likelihood of developing <jats:italic>Lg<\/jats:italic>-CL (ORadj=2.9 [95%CI 1.68\u20135.2]; <jats:italic>p<\/jats:italic>-value, 2.5\u00d710<jats:sup>\u22126<\/jats:sup>). Similarly, haplotype ACCCAAT (ORadj=2.7 [95%CI 1.5\u20134.7]; <jats:italic>p<\/jats:italic>-value, 3.2\u00d710<jats:sup>\u22125<\/jats:sup>) and haplotype AGCCGCC are associated with susceptibility to the development of <jats:italic>Lg<\/jats:italic>-CL (ORadj=1.7[95%CI 1.04\u20132.8]; <jats:italic>p<\/jats:italic>-value, 0.01). In our investigation, we also found a correlation between the genotypes of rs2069744, rs20541, rs1295685, rs847, and rs848 and plasma IL-5 levels among <jats:italic>Lg<\/jats:italic>-Cl patients. Furthermore, rs20541 showed a correlation with plasma IL-13 levels among <jats:italic>Lg<\/jats:italic>-Cl patients, while rs2069744 and rs848 showed a correlation with plasma IL-4 levels among the same group. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, our study identifies three haplotypes of <jats:italic>IL13<\/jats:italic> associated with resistance to disease development and three haplotypes linked to susceptibility. These findings suggest the possibility of a variant outside the gene region that may contribute, in conjunction with other genes, to differences in susceptibility and partially to the pathology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1232488","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:58:19Z","timestamp":1697439499000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A fine mapping of single nucleotide variants and haplotype analysis of IL13 gene in patients with Leishmania guyanensis-cutaneous leishmaniasis and plasma cytokines IL-4, IL-5, and IL-13"],"prefix":"10.3389","volume":"14","author":[{"given":"Jos\u00e9 do Esp\u00edrito Santo","family":"Junior","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josu\u00e9 Lacerda de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lener Santos da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cilana Chagas da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuanny Arruda do","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara L\u00facia Gomes de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyne Farias da","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline da Silva","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Pereira de Moura","family":"Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vinitius de Farias","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendranath","family":"Ramasawmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"B1","unstructured":"World Health Organisation. 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