Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazonia Legal (Rede Bionorte), Universidade do Estado do Amazonas, Manaus 69055038, Amazonas, Brazil.
Faculdade de Medicina, Universidade Nilton Lins, Manaus 69058030, Amazonas, Brazil.
Int J Mol Sci. 2024 Nov 19;25(22):12438. doi: 10.3390/ijms252212438.
Leishmaniasis, a disease caused by protozoan 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 -cutaneous leishmaniasis (-CL) patients with healthy individuals (HCs) by analyzing the genetic variants rs530537A>G, rs531542C>T, rs531604A>T and rs560880G>T. Additionally, a combined analysis of rs2043211A>T with rs530537 was performed. The genotype distribution for the four variants showed no significant differences between -CL patients and HCs. However, the haplotype analysis of the four variants identified the GTTT haplotype as associated with a 19% decreased likelihood of -CL development, suggesting a protective effect against disease progression. The combined analysis of with variants indicated that individuals homozygous for both variants (GG/TT) exhibited a 38% reduced risk of developing -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. may act as a genetic modifier in -CL.
利什曼病是一种由原生动物引起的疾病，表现出广泛的临床表现。宿主对感染的抵抗力或易感性通常受到与天然免疫相关的遗传构成的影响。半胱氨酸天冬氨酸蛋白酶-1（Caspase-1）是 NLRP3 炎性体的关键组成部分，对于将前体白细胞介素-1β（pro-IL-1β）加工成其活性形式白细胞介素-1β（IL-1β）至关重要，而 CARD8 作为 NLRP3 炎性体抑制剂发挥作用。我们通过分析 rs530537A>G、rs531542C>T、rs531604A>T 和 rs560880G>T 基因变异，对皮肤利什曼病（-CL）患者与健康对照者（HCs）进行了病例对照研究。此外，还对 rs2043211A>T 与 rs530537 的联合分析进行了研究。四个变体的基因型分布在 -CL 患者和 HCs 之间没有显示出显著差异。然而，对四个变体的单倍型分析表明，GTTT 单倍型与 -CL 发病几率降低 19%相关，提示对疾病进展具有保护作用。与 rs530537 的联合分析表明，与其他基因型组合相比，两个变体均为纯合子（GG/TT）的个体患 -CL 的风险降低了 38%（OR=0.62[95%CI：0.46-0.83]）。未发现 CASP1 变体基因型与血浆 IL-1β 水平之间存在相关性。可能在 -CL 中充当遗传修饰因子。
