State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Stroke. 2012 Jan;43(1):14-21. doi: 10.1161/STROKEAHA.111.625442. Epub 2011 Oct 27.
ANRIL encodes a long antisense noncoding RNA in the INK4 locus. Although ANRIL has been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke.
A Chinese case-control study was conducted, comprising 1657 cases (724 atherothrombosis, 466 lacunar infarction, and 462 hemorrhagic strokes) and 1664 controls. Stroke patients were prospectively followed-up for a median of 4.5 (range, 0.1-6.0) years. Expression of ANRIL transcripts was examined in 42 human atherosclerotic plaques.
After adjustment for vascular risk factors and correction for multiple comparisons, subjects carrying the GG genotype of rs10757278 had 1.47-fold (95% CI, 1.11-1.89; P=0.05) and 1.60-fold (95% CI, 1.16-2.15; P=0.04) increased risk for atherothrombotic and hemorrhagic strokes, respectively. During the follow-up, 317 recurrent strokes and 301 deaths from all causes were documented. Subjects carrying rs10757278GG had higher risk for stroke recurrence (relative risk [RR],1.56; 95% CI,1.15-2.12; P=0.005) and cardiovascular mortality (RR, 2.0; 95% CI, 1.26-3.18; P=0.003), respectively. Rs10757274 was also associated with stroke risk and recurrence. Family history of stroke further increased the stroke risk by 2.37-fold (95% CI, 1.38-4.06; P=0.01) and recurrent stroke risk by 2.45-fold (95% CI, 1.56-3.86; P<0.0001) respectively, when compared with those carrying none of G-alleles and without family history. Finally, rs10757278 was associated with differential expression of the ANRIL transcripts.
Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence.
ANRIL 编码 INK4 基因座上的长反义非编码 RNA。尽管已经证明 ANRIL 与冠心病有关，但它在中风中的作用并不一致，而且关于出血性中风的数据很少。
进行了一项中国病例对照研究，包括 1657 例病例（724 例动脉粥样硬化血栓形成、466 例腔隙性梗死和 462 例出血性中风）和 1664 例对照。前瞻性随访中风患者中位时间为 4.5 年（范围，0.1-6.0 年）。在 42 个人动脉粥样硬化斑块中检测了 ANRIL 转录本的表达。
在校正血管危险因素并校正多重比较后，携带 rs10757278 位点 GG 基因型的受试者发生动脉粥样硬化血栓形成和出血性中风的风险分别增加 1.47 倍（95%CI，1.11-1.89；P=0.05）和 1.60 倍（95%CI，1.16-2.15；P=0.04）。在随访期间，记录了 317 例复发性中风和 301 例全因死亡。携带 rs10757278GG 的受试者发生中风复发的风险更高（相对风险 [RR]，1.56；95%CI，1.15-2.12；P=0.005）和心血管死亡率（RR，2.0；95%CI，1.26-3.18；P=0.003）。rs10757274 也与中风风险和复发有关。中风家族史使中风风险增加 2.37 倍（95%CI，1.38-4.06；P=0.01），复发性中风风险增加 2.45 倍（95%CI，1.56-3.86；P<0.0001），与未携带任何 G 等位基因且无家族史的患者相比。最后，rs10757278 与 ANRIL 转录本的差异表达有关。
我们的研究结果表明，ANRIL 可能是动脉粥样硬化血栓形成和出血性中风及其复发的风险的新型遗传标志物。
