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

Leishmaniasis, a disease caused by protozoan <i>Leishmania</i> 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 <i>L. guyanensis</i>-cutaneous leishmaniasis (<i>Lg</i>-CL) patients with healthy individuals (HCs) by analyzing the <i>CASP1</i> genetic variants rs530537A>G, rs531542C>T, rs531604A>T and rs560880G>T. Additionally, a combined analysis of <i>CARD8</i>rs2043211A>T with <i>CASP1</i>rs530537 was performed. The genotype distribution for the four variants showed no significant differences between <i>Lg</i>-CL patients and HCs. However, the haplotype analysis of the four <i>CASP1</i> variants identified the GTTT haplotype as associated with a 19% decreased likelihood of <i>Lg</i>-CL development, suggesting a protective effect against disease progression. The combined analysis of <i>CARD8</i> with <i>CASP1</i> variants indicated that individuals homozygous for both variants (GG/TT) exhibited a 38% reduced risk of developing <i>Lg</i>-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. <i>CASP1</i> may act as a genetic modifier in <i>Lg</i>-CL.