Rs4612666 Polymorphism of the NLRP3 Gene Is Associated with the Occurrence of Large Artery Atherosclerotic Ischemic Strokes and Microembolic Signals

PURPOSE: Large artery atherosclerosis (LAA) ischemic stroke (IS) is the most common IS subtype, and microemboli are clinically important for indicating an increased risk of IS. Nucleotide-binding domain-like receptor protein 3 (NLRP3) plays a crucial role in the pathogenesis of atherosclerosis. The aim of this study is to investigate the relationship between NLRP3 gene polymorphisms and susceptibility for LAA IS and microembolic signals (MES) in the Chinese Han population. METHODS: We studied 293 patients diagnosed with LAA IS and 265 controls. Transcranial Doppler (TCD) was used to monitor the MES in all of the patients. Depending on the presence or absence of MES, the patients were divided into MES-positive and MES-negative subgroups. PCR-RFLP or direct sequencing were used to analyze three NLRP3 gene polymorphisms. RESULTS: Seventy-six patients presented with MES and the MES-positive rate was 25.94%. Logistic regression analysis showed that the TT genotype frequency for the rs4612666 gene polymorphism was higher in study patients than in the controls (adjusted P = 0.001) and higher in MES-positive patients compared to MES-negative patients (adjusted P = 0.015). The T allele of rs4612666 was associated with an increased risk for developing LAA IS and MES (P = 0.001; P = 0.015, resp.). Prevalence of the CCC haplotype was higher in the controls than in the patients (P = 0.009) and prevalence of the TGT haplotype was lower in the controls than in the patients (P = 0.019). CONCLUSIONS: The NLRP3 rs4612666 gene polymorphism may be related to the occurrence of LAA IS and MES, suggesting that the NLRP3 gene polymorphism increases the susceptibility of LAA IS by changing the plaque vulnerability.