Yan Ran, Qiu Xin, Dai Yalun, Jiang Yingyu, Gu Hongqiu, Jiang Yong, Ding Lingling, Cheng Si, Meng Xia, Wang Yilong, Zhao Xingquan, Li Hao, Wang Yongjun, Li Zixiao
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
J Cereb Blood Flow Metab. 2025 Feb;45(2):328-339. doi: 10.1177/0271678X241274681. Epub 2024 Aug 20.
Peroxisome proliferator-activated receptor-γ () plays a protective role against brain injury after stroke in mice. However, the relationship between gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in , rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, P = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.
过氧化物酶体增殖物激活受体γ（PPARγ）对小鼠中风后的脑损伤起保护作用。然而，PPARγ基因多态性与急性缺血性中风（AIS）功能结局之间的关系仍不清楚。对来自中国国家卒中登记系统三期（CNSR-III）的8822例患者进行全基因组测序后，进一步分析了PPARγ基因中的两个功能性单核苷酸多态性（SNP），即rs1801282 C＞G和rs3856806 C＞T。主要结局是三个月时的神经功能残疾。在这8822例患者中，分别有968例（11.0%）和3497例（39.6%）是rs1801282和rs3856806的携带者。rs3856806的携带者三个月时神经功能残疾风险降低（比值比[OR]，0.84；95%置信区间[CI]，0.73 - 0.98；p = 0.02），梗死体积增大的风险降低（OR 0.90，95% CI，0.81 - 0.99，p = 0.04）。仅在基线白细胞介素-6水平较低的情况下，他们的神经功能残疾风险也降低（OR 0.64，95% CI 0.48 - 0.84，P = 0.01）。rs1801282的携带者三个月时神经功能残疾风险降低（OR 0.77，95% CI，0.61 - 0.99，p = 0.04）。我们的研究表明，PPARγ基因多态性与AIS患者神经功能残疾风险降低及梗死体积增大有关。因此，PPARγ可能是AIS的一个潜在治疗靶点。
