Gonzalez-Pacheco Hector, Vargas-Alarcon Gilberto, Angeles-Martinez Javier, Martinez-Sanchez Carlos, Perez-Mendez Oscar, Herrera-Maya Gabriel, Martinez-Rios Marco Antonio, Peña-Duque Marco Antonio, Posadas-Romero Carlos, Fragoso Jose Manuel
Coronary Unit, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Atherosclerosis Study Group, Instituto Nacional de Cardiología Ignacio Chávez, México City, Mexico.
Immunol Res. 2017 Aug;65(4):862-868. doi: 10.1007/s12026-017-8924-0.
The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P = 0.006; OR = 0.61, 95%CI 0.44-0.84, P = 0.002; OR = 0.67, 95%CI 0.48-0.94, P = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.
NLRP3和CASP1基因的蛋白质产物参与前白细胞介素-1β（pro-IL-1B）和前白细胞介素-18（pro-IL-18）的裂解，从而产生活性细胞因子，这些细胞因子在急性冠状动脉综合征（ACS）的发展中起重要作用。本研究的目的是评估NLRP3和CASP1基因多态性是否为墨西哥人群中ACS易感性的生物标志物。通过5'核酸外切酶TaqMan分析对617例ACS患者和609例对照个体组成的一组人群进行了CASP1基因的两个多态性位点[G+7/in6A（rs501192）和A10370-G外显子6（rs580253）]以及NLRP3基因的一个多态性位点[UTR'3 G37562-C（rs10754558）]的基因分型。在隐性模型下，与健康对照相比，CASP1基因的G+7/in6A多态性与发生ACS的风险增加相关（比值比[OR]=1.76，95%置信区间[CI]为1.08-2.86，P=0.022）。同样，在隐性模型下，CASP1基因的A10370-G多态性与ACS风险增加相关（OR=1.75，95%CI为1.07-2.85，P=0.025）。此外，在共显性、显性、超显性和加性模型下，NLRP3基因的UTR'3 G37562-C多态性与ACS风险降低相关（OR=0.45，95%CI为0.22-0.92，P=0.006；OR=0.61，95%CI为0.44-0.84，P=0.002；OR=0.67，95%CI为0.48-0.94，P=0.02；以及OR=0.65，95%CI为0.50-0.94，P=0.02）。总之，本研究表明，CASP1基因的G+7/in6A和A10370-G多态性与发生ACS的风险增加相关，而NLRP3基因的UTR'3 G37562-C多态性与墨西哥人群中发生ACS的风险降低相关。
