Caspase-1 Variants and Plasma IL-1β in Patients with Leishmania guyanensis Cutaneous Leishmaniasis in the Amazonas

• Published in: International journal of molecular sciences Vol. 25; no. 22; p. 12438
• Main Authors: de Souza, Josué Lacerda, de Farias Guerra, Marcus Vinitius, de Mesquita, Tirza Gabrielle Ramos, Junior, José do Espírito Santo, Sequera, Hector David Graterol, da Silva, Lener Santos, da Silva, Larissa Almeida, Moura, Filipe Menezes, Menescal, Lizandra Stephanny Fernandes, da Costa Torres, Júlia, Pinheiro, Suzana Kanawati, Kerr, Herllon Karllos Athaydes, Ogusku, Mauricio Morishi, de Souza, Mara Lúcia Gomes, de Moura Neto, Jose Pereira, Sadahiro, Aya, Ramasawmy, Rajendranath
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 19-11-2024; MDPI
• Subjects: Genotype & phenotype; Haplotypes; Health care; Infections; Kinases; Parasites; Parasitic diseases; Plasma; Protozoa; Transcription factors; Brazil
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252212438

Leishmaniasis, a disease caused by protozoan Leishmania spp., exhibits a broad range of clinical manifestations. Host resistance or susceptibility to infections is often influenced by the genetic make-up associated with natural immunity. Caspase-1, a key component of the NLRP3 inflammasome, is critical for processing pro-IL-1β into its active form, IL-1β, while CARD8 functions as an NLRP3 inflammasome inhibitor. We conducted a case–control study comparing L. guyanensis-cutaneous leishmaniasis (Lg-CL) patients with healthy individuals (HCs) by analyzing the CASP1 genetic variants rs530537A>G, rs531542C>T, rs531604A>T and rs560880G>T. Additionally, a combined analysis of CARD8rs2043211A>T with CASP1rs530537 was performed. The genotype distribution for the four variants showed no significant differences between Lg-CL patients and HCs. However, the haplotype analysis of the four CASP1 variants identified the GTTT haplotype as associated with a 19% decreased likelihood of Lg-CL development, suggesting a protective effect against disease progression. The combined analysis of CARD8 with CASP1 variants indicated that individuals homozygous for both variants (GG/TT) exhibited a 38% reduced risk of developing Lg-CL (OR = 0.62 [95%CI:0.46–0.83]) in comparison to individuals with other genotype combinations. No correlation was found between the CASP1 variant genotypes and plasma IL-1β levels. CASP1 may act as a genetic modifier in Lg-CL.