摘要
目的探讨C反应蛋白(CRP)和生长停滞特异性基因产物6(GAS6)基因4个单核苷酸多态性(SNP)位点与缺血性脑卒中(IS)及其亚型的相关性,并进一步分析CRP和GAS6基因间的交互作用与IS及其亚型的相关性。方法采用回顾性病例对照研究,2010年10月—2012年12月连续收集129例IS患者作为病例组及192例非IS者作为对照组。采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)检测CRP rs3093059:T>C和rs1130864:C>T、GAS6 rs8191974:G>A和rs7400722:C>T 4个SNP位点的基因型,并结合DNA测序进行验证。检验4个SNP对IS发生的易患性,同时采用广义的多因素降维法(GMDR)研究二者之间的交互作用,并进一步运用Logistic回归模型进行验证。结果单位点分析显示,病例组及其亚型与对照组比较,基因型分布差异均无统计学意义(P>0.05);GMDR分析表明,在大动脉粥样硬化性脑卒中(LAA)发生中,CRP rs3093059:T>C与GAS6rs7400722:C>T的交互作用差异有统计学意义(检验样本一致性=61.29%;交叉验证一致性=10;P=0.0107)。同时携带rs3093059 TC+CC和rs7400722 CT+TT具有较高的LAA发生风险〔OR=2.439,95%CI(1.046,5.687),P=0.041〕。结论 CRP和GAS6基因可能共同参与影响了IS的易患性,二者之间的基因-基因交互作用将有助于为IS研究开辟新的领域。
Objective To investigate the association of four single nucleotide polymorphisms （SNP） sites of C - reac- tive protein （CRP） gene and growth arrest -specific gene 6 （GAS6） with ischemic stroke （IS） and its subtypes and the exist- ence of interactions between CRP gene and GAS6 gene in Chinese subjects. Methods A total of 129 patients with IS and 192 non - IS subjects were consecutively recruited between October 2010 and December 2012. Polymerase chain reaction - restrictive fragment length polymorphism （ PCR - RFLP ） and DNA sequencing were used to detect the genotype of the 4 SNP sites （ rs1130864 ： C 〉 T and rs3093059 ： T 〉 C in CRP; rs8191974 ： G 〉 A and rs7400722 ： C 〉 T in GAS6）. We assessed the as- sociations between IS risk and the 4 tagging SNP with χ2 text or Fisher＇s exact test. Their potential gene - gene interactions were evaluated by using the generalized multifactor dimensionality reduction （GMDR）. Logistic regression model was used for valida- tion. Results In the single - locus analysis, no significant difference was found between the group of patients with IS or its sub- types and the control group in the genotype of all variants （ P 〉 0. 05 ）. Moreover, the GMDR analysis suggested a significant two -locus interaction model involving CRP rs3093059 ： T 〉 C and GAS6 rs7400722 ： C 〉 T in large -artery atherosclerosis （LAA） （ testing accuracy = 61.29% ; cross validation consistency = 10 ; P = 0. 0107 ）. The individuals with combination of CRP rs3093059 Tr ＋ CC and GAS6 rs7400722 CT ＋ TF had a significantly higher risk of LAA [ OR = 2. 439, 95% CI （ 1. 046, 5. 687 ） ; P = 0. 041 ]. Conclusion The CRP and GAS6 genes may affect the susceptibility to IS through gene - gene interac- tions in Chinese subjects. The gene - gene interaction may be a novel area for IS research.
出处
《中国全科医学》
CAS
CSCD
北大核心
2013年第23期2709-2713,共5页
Chinese General Practice
基金
院级基金资助项目(201103)
