ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021
A Genome-wide Association Study Identifies SERPINB10, CRLF3, STX7, LAMP3, IFNG-AS1, and KRT80 As Risk Loci Contributing to Cutaneous Leishmaniasis in Brazil.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic analysis of IFNG-AS1 implicates opposite effects to Leishmania guyanensis-cutaneous leishmaniasis: rs4913269 confers protection while rs7134599 enhances susceptibility and correlates with high plasma IL-4 and IL-10 levels.PLoS neglected tropical diseases · 2025Article
- Cytokine Receptor-like Factor 3 (CRLF3) and Its Emerging Roles in Neurobiology, Hematopoiesis and Related Human Diseases.International journal of molecular sciences · 2025Review
- Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis.Microorganisms · 2025Article
- The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer.Cancer biology & therapy · 2024Article
- Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis.Frontiers in cellular and infection microbiology · 2024Article
- KRT80 expression works as a biomarker and a target for differentiation in gastric cancer.Histology and histopathology · 2024Article
- Article
- The cytokine receptor CRLF3 is a human neuroprotective EV-3 (Epo) receptor.Frontiers in molecular neuroscience · 2023Article
- Malaria and leishmaniasis: Updates on co-infection.Frontiers in immunology · 2023Review
- Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM.Frontiers in genetics · 2023Article
- LncRNA: A Potential Target for Host-Directed Therapy ofPharmaceutics · 2022Review
- Increased Expression of SERPINB10 Associated with Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.Disease markers · 2022Article
- Cytokine Receptor-Like Factor 3 (CRLF3) Contributes to Early Zebrafish Hematopoiesis.Frontiers in immunology · 2022Article
- SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells.Respiratory research · 2021Article
- Human genetics of leishmania infections.Human genetics · 2020Review
- Genetics, Transcriptomics and Meta-Taxonomics in Visceral Leishmaniasis.Frontiers in cellular and infection microbiology · 2020Review
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundOur goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.
methodsGenotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4 498 586 imputed single-nucleotide variants (SNVs). A genome-wide association study (GWAS) using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL) and chromatin interaction mapping was performed in Functional Mapping and Annotation (FUMA). Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.
resultsPositional mapping identified 32 genomic loci associated with CL, none achieving genome-wide significance (P < 5 × 10-8). Lead SNVs at 23 loci occurred at protein coding or noncoding RNA genes, 15 with eQTLs for functionally relevant cells/tissues and/or showing differential expression in lesions. Of these, the 6 most plausible genetic risk loci were SERPINB10 (Pimputed_1000G = 2.67 × 10-6), CRLF3 (Pimputed_1000G = 5.12 × 10-6), STX7 (Pimputed_1000G = 6.06 × 10-6), KRT80 (Pimputed_1000G = 6.58 × 10-6), LAMP3 (Pimputed_1000G = 6.54 × 10-6), and IFNG-AS1 (Pimputed_1000G = 1.32 × 10-5). LAMP3 (Padjusted = 9.25 × 10-12; +6-fold), STX7 (Padjusted = 7.62 × 10-3; +1.3-fold), and CRLF3 (Padjusted = 9.19 × 10-9; +1.97-fold) were expressed more highly in CL biopsies compared to normal skin; KRT80 (Padjusted = 3.07 × 10-8; -3-fold) was lower. Multiple cis-eQTLs across SERPINB10 mapped to chromatin interaction regions of transcriptional/enhancer activity in neutrophils, monocytes, B cells, and hematopoietic stem cells. Those at IFNG-AS1 mapped to transcriptional/enhancer regions in T, natural killer, and B cells. The percentage of peripheral blood CD3+ T cells making antigen-specific interferon-γ differed significantly by IFNG-AS1 genotype.
conclusionsThis first GWAS for CL identified multiple genetic risk loci including a novel lead to understanding CL pathogenesis through regulation of interferon-γ by IFNG antisense RNA 1.
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