The Association between Polymorphism of NLRP3 rs10754558 and Susceptibility to Arteriosclerosis Obliterans in Chinese Han Male Population

Background and aims: Cholesterol crystals have been proved to be able to cause inflammation. NLRP3 inflammasome is activated in response to the accumulation of cholesterol crystals to produce IL-1β, which is associated with atherosclerotic lesions. NLRP3, as part of innate immunity, is involved in the regulation of inflammatory activity described above. The main objective of this study was to investigate the relationship between the polymorphism of NLRP3 rs10754558 and the susceptibility to arteriosclerosis obliterans (ASO) in Chinese Han males. Methods: The NLRP3 rs10754558 genotype was detected by the TaqMan allele assays in 758 male patients suffered from arteriosclerosis obliteration and 793 male controls. Blood glucose, total cholesterol (TC), triglyceride (TG), urea nitrogen, creatinine, serum uric acid, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and IL-1β were detected in all subjects. Clinical data were recorded and genotype-phenotype was analyzed. Independent sample T test was used for comparison between the two groups. The odds ratio (ORs) with 95% confidence interval (CIs) was calculated to show the strength of the relationship between the genotype distribution or allele frequencies and ASO. Genotype-phenotype analysis was performed in ASO patients by ANOVA. Results: The frequencies of genotype and allele in ASO group were significantly different from that in control group (p = 0.022 by genotype, p = 0.003 by allele). People who were carrying genotype GG had a higher risk for ASO than those carrying genotype CC (OR=1.574,95％CI 1.161-2.135,P=0.003) ,which was still significant after the adjustment of the history of smoking, TC, LDL, fasting blood glucose, systolic blood pressure and BMI(OR=1.448,95％CI 1.046-1.461,P=0.004). Moreover, there was an interaction between rs10754558 of NLRP3 and rs2043211 of CARD8 gene. Under the premise of carrying the T allele of CARD8 rs2043211, the G allele of NLRP3 rs10754558 increases the susceptibility to ASO. This gene-gene interaction is consistent with IL-1β levels. Conclusion: Our finding suggests the polymorphisms of NLRP3 rs10754558 are probably associated with the development of ASO in Chinese Han male population. And there may be an interaction between rs10754558 of NLRP3 and rs2043211 of CARD8 gene in the development of ASO.