中国人染色体3q22．3区基因多态性与缺血性卒中的关系

目的探讨染色体3q22．3区基因多态性与缺血性卒中及其亚型的关系。方法采用病例对照研究方法。卒中组为2012年6-12月在南京卒中注册系统中连续注册的377例缺血性卒中患者，按急性卒中治疗org10172试验（TOAST）分型将患者分类；对照组为246名年龄、性别相匹配的健康者。采用改良多重连接酶反应技术确定基因型。分析的单核苷酸多态位点（SNP）包括rs2293252、rsl2631438及rsl0935282。应用Haploview4．2软件进行连锁不平衡检验。采用Phase软件进行单倍型分析。结果①rs2293252和rsl0935282位点基因型均为GG、GA、AA。rsl2631438位点基因型为CC、CT、TT。②卒中组与对照组比较，3个SNP位点的基因型频率及等位基因频率差异均无统计学意义（P〉0．05）。卒中组中，大动脉粥样硬化性（LAA）卒中患者rs12631438位点CC基因型频率分别为17．7％（25/141）与9．3％（23/246）]和C等位基因频率分别为41．1％（116/282）与32．5％（160/492）]均高于对照组；其他卒中亚型与对照组差异无统计学意义。多因素Logistic回归分析显示，CC基因型与LAA卒中相关（OR=2．03，95％CI：1．08～3．91，P=0．040）。③对3个位点的单倍型分析发现，LAA卒中患者rs2293252-rsl2631438位点的A-C单倍型频率高于对照组分别为16．7％（47/282）与10．4％（51/492）；OR=1．81，95％CI：1．16～2．80，P=0．008]，rsl0935282．rsl2631438位点的A-C单倍型频率也高于对照组分别为9．9％（28/282）与4．5％（22/492）；OR=2．56，95％C／：1．41～4．64，P=0．001]。结论中国汉族人群染色体3q22．3区的rsl2631438位点多态性可能与LAA卒中相关。rs2293252-rs12631438和rsl0935282-rsl2631438位点A—C单倍型可能是发生LAA卒中的危险因素。

Relationship between chromosome 3q22.3 gene polymorphisms and ischemic stroke in Chinese

Objective To investigate the relationship between chromosome 3q22. 3 gene polymorphisms and ischemic stroke with its subtypes. Methods A case-control study was conducted in the study. The case group was 377 consecutive patients with ischemic stroke registered in the Nanjing Stroke Registry Program from June 2012 to December 2012. The patients were classified according to TOAST classification. The control group was 246 age- and sex-matched healthy subjects. The genotypes were determined with the improved multiplex ligase chain reaction. Single nucleotide of polymorphism （SNP） was analyzed, including rs2293252, rs12631438, and rs10935282. The Haploview 4.2 software was used to conduct linkage disequilibrium. Phase software was used to conduct haplotype analysis. Results ①The rs2293252 and rs10935282 loci genotypes were GG, GA, and AA. The rs12631438locus genotypes were CC, CT, and TT. ② Compared to the control group, there were no significant differences in genotype frequencies and allele frequencies of three SNP loci in the case group （ P 〉 0.05 ）. The frequency of CC genotype on rs12631438 locus （17.7% 25/141 ] vs. 9.3% 23/246] ） and C allele frequency （ 41.1% 116/282 ] vs. 32.5 % 160/492 ] ） in patients with large artery atherosclerotic （LAA） stroke were higher than those in the control group. There were no significant differences for the comparement of the other stroke subtypes. Multivariate Logistic regression analysis showed that the CC genetype was associated with LAA stroke （ OR = 2.03, 95 % CI 1.08 -3.91 ,P = 0. 040）. ③The haplotype analysis of these three loci found that the frequencies of A-C haplotype on rs2293252-rs12631438 loci in patients with LAA were higher than those in the control group （ 16.7% vs. 10.4% , OR = 1.81, 95% CI 1. 16 -2. 80, P = 0. 008 ） . The frequencies of A-C haplotype on rs10935282- rs12631438 loci were also higher than those in the control group （9.9% vs. 4.5% ; OR = 2.56, 95% CI 1.41 -4.64,P = 0.001）. Condusions Gene polymorphisms of rs12631438 located in chromosome 3q22. 3 region in Chinese Han population may be associated with LAA stroke. The A-C haplotype on rs2293252-rs12631438 and rs10935282-rs12631438 loci may be a risk factor for LAA stroke.