UGT1A6单核苷酸多态性与缺血性卒中患者阿司匹林低反应性的关联性研究  

Relationship between single nucleotide polymorphisms of UGT1A6 and aspirin low responsiveness in patients with ischemic stroke

作　　者：刘柯婷 周淑宇 蔡必扬 曹琴琴[1] 刘新峰[1] 

机构地区：[1]南京军区南京总医院神经内科,210002 [2]四川省自贡市第一人民医院神经内科

出　　处：《中华神经科杂志》2016年第10期775-779,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金-重大国际（地区）合作研究项目（81220108008）

摘　　要：目的研究UGT1A6单核苷酸多态性（SNPs）与阿司匹林反应性的关系。方法连续纳入2011年9月至2014年10月在南京卒中注册系统注册的缺血性卒中患者。运用血栓弹力图检测所有入组患者血小板功能，采用改进的多重连接酶反应技术检测患者基因型。采用广义线性模型分析SNPs与阿司匹林反应性之间的相关性。结果共纳入323例缺血性卒中患者，广义线性模型分析发现，rs2070959的显性模型（p=0．084，P=0．010，P校正=0．029）和加性模型（β=0．060，P=0．033）都与血小板抑制率呈显著的正相关。男性患者中，显性模型β=0．098，P=0．006，P校正=0．01；加性模型β=0．072，P=0．024。表明显性模型中，该位点的野生型个体（AA）较含突变基因的个体（GA、GG）发生阿司匹林低反应性的风险更高。结论UGT1A6基因rs2070959位点基因多态性与缺血性卒中患者阿司匹林低反应性相关，其野生型患者（AA）较含突变基因的患者（GA、GG）发生阿司匹林低反应性的风险增高，这种关系在男性患者中尤为显著。因此检测与阿司匹林代谢相关的基因多态性或实验室检测血小板功能可能有助于临床医师为缺血性卒中患者制定个体化抗血小板治疗方案。Objective To investigate the relationship between single nucleotide polymorphisms （SNPs） of UGT1A6 and aspirin response in a cohort of Chinese Han population. Methods A total of 323 ischemie stroke patients consecutively registered in Nanjing Stroke Registry Program from September 2011 to October 2014 were enrolled. Three SNPs （ rs6759892, rs2070959 and rs1105879 ） of UGT1A6 were genotyped in these ischemic stroke patients. Association of genotypes and aspirin response was evaluated by generalized linear model. Indicated with the inhibition rate of platelets, aspirin response was assessed by thromboelastograph. Results The mutation allele （G） of rs2070959 was positively related to platelets inhibition （β =0. 084, P =0. 010, P a =0. 029）, especially in male （β=0. 098, P=0. 006, Pa =0. 019）. The dominant models of rs6759892, rs1105879 were also modestly related to aspirin response （P=0.015, Pa =0.046 in both SNPs） in male. Thus the polymorphisms of UGT1A6 showed a relationship with aspirin response, especially in males. Conclusions The results indicated that genetic polymorphism of UGT1A6 might have an effect on individuals＇ aspirin response, especially in males. These findings can help clinicians to optimize the antiplatelet therapy for ischemie stroke patients.

关 键 词：缺血性卒中 阿司匹林低反应性 尿苷二磷酸葡萄糖醛酸基转移酶 

分 类 号：R743.3[医药卫生—神经病学与精神病学]