Huan Cai1, Biyang Cai2, Lingli Sun2, Hao Zhang2, Shuyu Zhou2, Liping Cao3, Hongquan Guo2, Wen Sun2, Bernard Yan4, Stephen M Davis4, Zhizhong Zhang5, Xinfeng Liu6. 1. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, Jiangsu, China. 2. Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu, China. 3. Department of Neurology, The First People's Hospital of Changzhou, Changzhou 213000, Jiangsu, China. 4. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia. 5. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, Jiangsu, China. Electronic address: zhizhongn@gmail.com. 6. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, Jiangsu, China. Electronic address: xfliu2@vip.163.com.
Abstract
PURPOSE: Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. METHODS: A total of 617 ischemic stroke patients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. RESULTS: Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status (Pinteraction=0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance (Pinteraction=0.040). CONCLUSIONS: In Chinese Han stroke patients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin.
PURPOSE:Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. METHODS: A total of 617 ischemic strokepatients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. RESULTS: Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status (Pinteraction=0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance (Pinteraction=0.040). CONCLUSIONS: In Chinese Han strokepatients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin.