The Journal of infectious diseases · 2026
Epistatic Interactions Among Inflammasome Gene Variants Are Associated with Reduced Risk of Paracoccidioidomycosis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
da Silva Coelho Sanderson, Amorim Bárbara Casella, Ramos Jeferson Vidart, da Costa Marques Ana Paula, de Oliveira Sandra Maria do Valle Leone, Pereira-Latini Ana Carla, de Souza Vânia Nieto Brito, de Rezende Romera Grazielli Rocha, de Melo Dayane Alves, de Albuquerque Viviane Lima, Pontillo Alessandra, Soares Pereira Beatriz Aparecida, de Souza Cavalcante Ricardo, Mendes Rinaldo Poncio, Paniago Anamaria Mello Miranda, Fava Wellington Santos, Venturini James
Аннотация
BACKGROUND: Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America with marked clinical heterogeneity, suggesting a role for host immunogenetic factors. The NLRP3 inflammasome and IL-1β signaling are important in antifungal immunity, but human genetic evidence remains limited. We evaluated whether single-nucleotide variants (SNVs) in inflammasome-related genes (NLRP1, NLRP3, CARD8, CASP1, and IL1B) are associated with PCM susceptibility, clinical form, and disease severity, including gene-gene interactions.
METHODS: We conducted a case-control study including 346 individuals (154 PCM patients and 192 gp43-reactive healthy controls). Genetic associations were tested under multiple inheritance models using logistic regression adjusted for age, sex, smoking, and alcoholism. Epistatic interactions were assessed within the inflammasome-IL-1β axis, with Firth penalized logistic regression as a sensitivity analysis.
RESULTS: No single-SNV association with PCM susceptibility, clinical form, or severity remained significant after multiple-testing correction. Pairwise epistasis analysis identified an interaction between NLRP3 rs10754558 and IL1B rs1143634 associated with reduced PCM susceptibility (OR = 0.34; 95% CI: 0.17-0.69; pFDR = 0.015), supported by Firth regression. No significant epistatic interactions were found for clinical form or severity.
CONCLUSIONS: Genetic interactions within the inflammasome-IL-1β axis may contribute to PCM susceptibility. The interaction between NLRP3 rs10754558 and IL1B rs1143634 warrants validation in larger, independent cohorts.
METHODS: We conducted a case-control study including 346 individuals (154 PCM patients and 192 gp43-reactive healthy controls). Genetic associations were tested under multiple inheritance models using logistic regression adjusted for age, sex, smoking, and alcoholism. Epistatic interactions were assessed within the inflammasome-IL-1β axis, with Firth penalized logistic regression as a sensitivity analysis.
RESULTS: No single-SNV association with PCM susceptibility, clinical form, or severity remained significant after multiple-testing correction. Pairwise epistasis analysis identified an interaction between NLRP3 rs10754558 and IL1B rs1143634 associated with reduced PCM susceptibility (OR = 0.34; 95% CI: 0.17-0.69; pFDR = 0.015), supported by Firth regression. No significant epistatic interactions were found for clinical form or severity.
CONCLUSIONS: Genetic interactions within the inflammasome-IL-1β axis may contribute to PCM susceptibility. The interaction between NLRP3 rs10754558 and IL1B rs1143634 warrants validation in larger, independent cohorts.