中文摘要：

目的：在缺血性卒中家系中探讨PDE4D基因rs966221位点多态性与缺血性卒中及其相关性状的关系。方法：采用家系研究设计,应用广义估计方程（generalized estimating equation,GEE）进行多因素的回归分析,并用非参数连锁分析和以家系为基础的关联检验（family based association test,FBAT）进行连锁和关联分析。结果：共纳入276个缺血性卒中家系,776名研究对象。应用GEE控制混杂因素并调整家系内部相关性后,载脂蛋白B、颈动脉内膜中层厚度、高密度脂蛋白胆固醇及血压水平与缺血性卒中相关（P〈0.05）。非参数连锁分析和FBAT分析均未发现rs966221位点多态性与缺血性卒中相关,但该位点与卒中相关的数量性状存在连锁和关联关系。非参数连锁分析发现,在调整可能的混杂因素后,rs966221位点与载脂蛋白B（P〈0.001）、超敏C反应蛋白水平（P=0.003）、收缩压（P=0.036）存在连锁;在调整高脂血症、高血压等疾病的患病状态后,rs966221位点TT基因型（P=0.019）和CT基因型（P=0.007）与颈动脉内膜中层厚度相关,显性模型中C等位基因与颈动脉内膜中层厚度具有统计学关联（P=0.019）。结论：血脂、血压的异常以及颈动脉内膜中层增厚与缺血性卒中相关,PDE4D基因rs966221位点与载脂蛋白B、超敏C反应蛋白及收缩压水平存在连锁,该位点C等位基因与颈动脉内膜中层厚度具有统计学关联。

英文摘要：

Objective： To investigate the PDE4D gene with stroke and related traits in linkage and association between rs966221 （SNP 83 ） in ischemic stroke families. Methods： Ischemic stroke families including ischemic stroke patients and their siblings and/or parents were recruited. Generalized estimating equation （GEE） was used to adjust for with-in family correlations and other potential confounding factors. Non-parameter linkage analysis and family based association test （FBAT） were applied to ex- plore the relationship between rs966221 polymorphism and ischemic stroke together with its related traits. Results： In the study 276 ischemic stroke families with totally 776 participants were enrolled. Apolipoprotein B （apoB）, carotid intima media thickness （cIMT）, high-density lipoprotein cholesterol and blood pressure were associated with ischemic stroke. In family based association test, after being adjusted for related chronic diseases, rs966221 C allele was found to be associated with cIMT in the dominant model （P =0. 019 ）, TF genotype （ P = 0. 019 ） and CT genotype （ P = 0. 007 ） were associated with cIMT significantly. After being adjusted for potential confounding factors, evidence of linkage was observed for rs966221 with apoB （ P 〈 0. 001 ）, high-sensitivity C-reactive protein （ P = 0. 003 ） and systolic blood pressure （P = 0. 036）. Conclusion： Abnormal serum lipid, blood pressure and increasing cIMT were associated with ischemic stroke, and linkage was observed for with apoB, high-sensitivity Creactive protein, and systolic blood pressure; rs966221 C allele was probably associated with cIMT.