Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, Beijing, 100037, China.
J Mol Neurosci. 2014 Jun;53(2):196-203. doi: 10.1007/s12031-014-0283-x. Epub 2014 Mar 25.
Type III collagen plays an important role in activating platelets, forming thrombus, and maintaining the mechanical properties of arteries. This study aimed to test the hypothesis that genetic variants of COL3A1 (gene encoding type III collagen) contribute to recurrence and prognosis of stroke. We investigated the associations of three variants (rs2138533, rs11887092, and rs1800255) in the COL3A1 gene with stroke recurrence and prognosis in 1,544 patients with three subtypes of stroke: lacunar infarction (n = 442), atherothrombotic infarction (n = 670), and hemorrhage (n = 432). These associations were evaluated by Kaplan-Meier analysis and Cox regression models. Patients were followed up for 4.5 years. The A allele of rs1800255 in the COL3A1 gene coding region was significantly associated with a reduced risk of stroke recurrence in patients with lacunar infarction (adjusted hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36-0.93, P = 0.024), but there was an increased risk of all-cause mortality of atherothrombotic patients (adjusted HR 1.43, 95 % CI 1.01-2.00, P = 0.044). The TT genotype of rs2138533 showed a significantly increased risk of death caused by cardiovascular disease or stroke in lacunar infarct patients (adjusted HR 2.98, 95 % CI 1.27-6.98, P = 0.012), but there was a reduced risk of all-cause mortality for patients with intracerebral hemorrhage (adjusted HR 0.34, 95 % CI 0.12-0.93, P = 0.036). The G allele of rs11887092 increased the risk of stroke recurrence in patients with atherothrombotic stroke (adjusted HR 1.59, 95 % CI 1.04-2.44, P = 0.035). In conclusion, variants of COL3A1 might play a vital role in determining the risk of recurrence and prognosis after stroke.
III 型胶原在激活血小板、形成血栓和维持动脉的机械性能方面发挥着重要作用。本研究旨在检验 COL3A1（编码 III 型胶原的基因）的遗传变异是否有助于中风复发和预后的假设。我们研究了 COL3A1 基因中的三个变体（rs2138533、rs11887092 和 rs1800255）与 1544 名中风患者的中风复发和预后的关系，这些患者分为三种亚型：腔隙性梗死（n=442）、动脉粥样硬化血栓性梗死（n=670）和出血性梗死（n=432）。通过 Kaplan-Meier 分析和 Cox 回归模型评估这些关联。患者的随访时间为 4.5 年。COL3A1 基因编码区 rs1800255 的 A 等位基因与腔隙性梗死患者中风复发风险降低显著相关（调整后的危险比[HR]0.58，95%置信区间[CI]0.36-0.93，P=0.024），但动脉粥样硬化性患者全因死亡率增加（调整后的 HR 1.43，95%CI 1.01-2.00，P=0.044）。rs2138533 的 TT 基因型在腔隙性梗死患者中显著增加了心血管疾病或中风导致的死亡风险（调整后的 HR 2.98，95%CI 1.27-6.98，P=0.012），但颅内出血患者的全因死亡率降低（调整后的 HR 0.34，95%CI 0.12-0.93，P=0.036）。rs11887092 的 G 等位基因增加了动脉粥样硬化性中风患者中风复发的风险（调整后的 HR 1.59，95%CI 1.04-2.44，P=0.035）。总之，COL3A1 的变体可能在决定中风后复发和预后的风险方面发挥着重要作用。
