A Polymorphism Within the 3′UTR of NLRP3 is Associated with Susceptibility for Ischemic Stroke in Chinese Population

A Polymorphism Within the 3′UTR of NLRP3 is Associated with Susceptibility for Ischemic Stroke in Chinese Population

Cellular and Molecular Neurobiology, December 2015

26689701

Zhansheng Zhu, Jing Yan, Chunsong Geng, Dagang Wang, Chaoyang Li, Shuai Feng, Huiping Wang

Stroke was regarded as a severe disorder with high morbidity and high mortality worldwide, ischemic stroke (IS) accounts for 85 to 90 % of new increased stroke cases. Partial mechanisms were elucidated by genetic factors including genomic instability such as single nucleotide polymorphism (SNP). Previous reports demonstrated that inflammation was involved in IS, NLRP3 [nucleotide-binding domain (NOD)-like receptor protein 3], acting as a specific inflammatory gene, however, its function and influence on IS was not well clarified. In this study, a case-control study including 1102 IS patients and 1610 healthy controls was conducted to investigate the association between IS susceptibility with a SNP (rs10754558) in 3'UTR of NLRP3. Logistic regression analysis showed that the heterozygote and the homozygote GG confer a significantly increased risk of CRC after controlling for other covariates (adjusted OR = 1.52, 95 % C.I. 1.19-1.97, P = 0.002; adjusted OR = 2.22, 95 % C.I. 2.18-3.67, P < 0.001, respectively). Carriage of G allele was associated with a greatly increased risk of developing the disease (OR = 1.69, 95 % C.I. 1.31-1.83, P < 0.001). Stratification analysis found that hypertension had interaction with rs10754558 to modulate IS risk. Further in vitro assay revealed that rs10754558 can affect mRNA level of NLRP3, suggesting its possible functional significance. Our data suggested that genetic polymorphisms in NLRP3 may influence IS risk in Chinese population. Replication of our studies in other populations and further functional studies are required for complete comprehension of the roles of NLRP3 polymorphisms in IS risk.