Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, PR China.
Cerebrovasc Dis. 2012;33(6):558-65. doi: 10.1159/000338781. Epub 2012 Jun 8.
The association between polymorphism -1131T/C in the promoter region of apolipoprotein A5 (APOA5) and ischemic stroke and plasma triglyceride (TG) levels remains controversial. To better clarify the association between APOA5-1131T/C and risk of ischemic stroke and plasma TG levels, we performed a meta-analysis to examine the allele and genotype of APOA5-1131T/C polymorphism in ischemic stroke cases and controls.
Based on the search of PubMed, Embase, MEDLINE, CNKI (National Knowledge Infrastructure) and CBM (Chinese BioMedical Literature Database) databases, we identified and abstracted outcome data from all articles to evaluate the association between APOA5 and ischemic stroke/plasma TG levels. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed in dominant model (CC + TC vs. TT), recessive model (CC vs. TC + TT), homozygote comparison (CC vs. TT) and heterozygote comparison (TC vs. TT). The association between dominant model (CC + TC vs. TT) and plasma TG/total cholesterol/high-density lipoprotein cholesterol levels was measured by a weighted mean difference (WMD) with its corresponding 95% CI. To evaluate the ethnicity-specific effects, subgroup analyses were performed by ethnic group.
A meta-analysis containing 2,294 ischemic stroke cases and 1,858 controls from 8 case-control studies was performed. The results showed that APOA5-1131T/C polymorphism was significantly associated with ischemic stroke in all comparison models (CC + TC vs. TT, OR = 1.70, 95% CI = 1.24-2.32; CC vs. TC + TT, OR = 1.36, 95% CI = 0.98-1.90; CC vs. TT, OR = 1.73, 95% CI = 1.34-2.23; TC vs. TT, OR = 1.67, 95% CI = 1.19-2.36). On subgroup analysis by ethnicity, similarly significant associations were found in both Asians and Europeans, and the Europeans possessed a higher risk of ischemic stroke, especially in CC versus TT model (OR = 4.47, 95% CI = 1.33-15.06). Significant association between the C allele and elevated TG levels was detected in both ischemic stroke cases and controls; the TG levels were higher in the ischemic stroke cases and controls carrying the APOA5-1131C allele than in the noncarriers (CC + TC vs. TT, cases WMD = 0.43, 95% CI = 0.27-0.59; controls WMD = 0.51, 95% CI = 0.35-0.66). Similar within-group comparison of the total cholesterol and high-density lipoprotein cholesterol levels did not show any difference.
Our meta-analysis revealed that the APOA5-1131T/C polymorphism is associated with a significant risk of ischemic stroke and elevated TG levels. The CC genotype and C allele might be a genetic risk factor that increases susceptibility of ischemic stroke and elevates plasma TG levels, and might be a useful target for clinical therapeutic intervention.
载脂蛋白 A5（APOA5）启动子区域 -1131T/C 多态性与缺血性卒中及血浆甘油三酯（TG）水平之间的关联仍存在争议。为了更好地阐明 APOA5-1131T/C 与缺血性卒中风险和血浆 TG 水平之间的关联，我们进行了一项荟萃分析，以检查 APOA5-1131T/C 多态性在缺血性卒中病例和对照中的等位基因和基因型。
基于对 PubMed、Embase、MEDLINE、CNKI（国家知识基础设施）和 CBM（中国生物医学文献数据库）数据库的检索，我们从所有文章中识别和提取了结局数据，以评估 APOA5 与缺血性卒中/血浆 TG 水平之间的关联。在显性模型（CC+TC vs. TT）、隐性模型（CC vs. TC+TT）、纯合子比较（CC vs. TT）和杂合子比较（TC vs. TT）中进行了合并优势比（OR）及其 95%置信区间（CI）。通过加权均数差（WMD）及其相应的 95%CI 来衡量显性模型（CC+TC vs. TT）与血浆 TG/总胆固醇/高密度脂蛋白胆固醇水平之间的关联。为了评估种族特异性效应，我们按种族进行了亚组分析。
我们进行了一项荟萃分析，纳入了来自 8 项病例对照研究的 2294 例缺血性卒中病例和 1858 例对照。结果表明，APOA5-1131T/C 多态性与所有比较模型中的缺血性卒中均显著相关（CC+TC vs. TT，OR=1.70，95%CI=1.24-2.32；CC vs. TC+TT，OR=1.36，95%CI=0.98-1.90；CC vs. TT，OR=1.73，95%CI=1.34-2.23；TC vs. TT，OR=1.67，95%CI=1.19-2.36）。按种族进行亚组分析时，在亚洲人和欧洲人中均发现了类似的显著关联，欧洲人缺血性卒中的风险更高，尤其是在 CC 与 TT 模型中（OR=4.47，95%CI=1.33-15.06）。在缺血性卒中病例和对照中均检测到 C 等位基因与 TG 水平升高之间存在显著关联；携带 APOA5-1131C 等位基因的缺血性卒中病例和对照的 TG 水平高于非携带者（CC+TC vs. TT，病例 WMD=0.43，95%CI=0.27-0.59；对照 WMD=0.51，95%CI=0.35-0.66）。在总胆固醇和高密度脂蛋白胆固醇水平的组内比较中未发现任何差异。
我们的荟萃分析表明，APOA5-1131T/C 多态性与缺血性卒中及 TG 水平升高显著相关。CC 基因型和 C 等位基因可能是增加缺血性卒中易感性和升高血浆 TG 水平的遗传风险因素，可能是临床治疗干预的有用靶点。
