Setzer Matthias, Hermann Elvis, Seifert Volker, Marquardt Gerhard
Department of Neurosurgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
Spine (Phila Pa 1976). 2008 Mar 1;33(5):497-502. doi: 10.1097/BRS.0b013e3181657cf7.
Prospective evaluation of apolipoprotein E (APOE) genotypes in 106 consecutive patients with stenosis of the cervical spinal canal.
To determine the association between cervical spondylotic myelopathy (CSM) in patients with chronic spinal cord compression and the APOE genotype.
The APOE allele epsilon 4 is a risk factor for the occurrence, progression, and poor outcome in several neurologic diseases. Information of the association between APOE genotype and CSM in the literature are lacking so far.
One hundred six consecutive patients with chronic cervical spinal cord compression due to stenosis of the spinal canal were evaluated prospectively. APOE genotypes were determined by polymerase chain reaction followed by restriction enzyme digestion and sodiumdodecylsulfate poyacrylamide gel electrophoresis (SDS PAGE) of digested fragments. Clinical and radiologic variables evaluated were age, occurrence of CSM, duration of symptoms, number of affected segments, and diameter of spinal canal of most affected segment. Univariate association between variables was tested. A backward stepwise method was used to construct multivariate logistic regression models in relation to the occurrence of CSM as dependent variable.
The following distribution of APOE genotypes was found: epsilon 2 epsilon 2 3 patients (2.8%), epsilon 2 epsilon 3 9 patients (8.5%), epsilon 2 epsilon 4 1 patient (0.9), epsilon 3 epsilon 3 67 patients (63.2%), epsilon 3 epsilon 4 24 patients (22.6%), epsilon 4 epsilon 4 2 patients (1.9%). Univariate analysis showed that patients with chronic spinal cord compression and homo- or heterozygous allele epsilon 4 are more likely to develop CSM than patients without allele epsilon 4 (65.0% vs. 35.0%, P < 0008; OR 3.5; 95% CI 1.3-9.8). This effect remained significant in a binary logistic regression model adjusted to other known risk factors for CSM. Inclusion of the variable homo- or heterozygous epsilon 4 allele led to an increased goodness of fit of the model compared with the model without epsilon 4. CONCLUSION.: This study supports the hypothesis that the APOE epsilon 4 allele increases the risk of CSM in patients with chronic cervical spinal cord compression; however, a larger prospective population-based study is needed to answer this question definitively.
对106例连续性颈椎管狭窄患者的载脂蛋白E(APOE)基因型进行前瞻性评估。
确定慢性脊髓压迫患者的脊髓型颈椎病(CSM)与APOE基因型之间的关联。
APOEε4等位基因是几种神经系统疾病发生、进展及预后不良的危险因素。目前文献中缺乏APOE基因型与CSM之间关联的信息。
对106例因椎管狭窄导致慢性颈椎脊髓压迫的连续性患者进行前瞻性评估。通过聚合酶链反应,随后对消化片段进行限制性酶切和十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)来确定APOE基因型。评估的临床和放射学变量包括年龄、CSM的发生情况、症状持续时间、受累节段数以及最受累节段的椎管直径。对变量之间的单因素关联进行检验。采用向后逐步法构建以CSM发生情况为因变量的多因素逻辑回归模型。
发现APOE基因型的分布如下:ε2ε2 3例患者(2.8%),ε2ε3 9例患者(8.5%),ε2ε4 1例患者(0.9%),ε3ε3 67例患者(63.2%),ε3ε4 24例患者(22.6%),ε4ε4 2例患者(1.9%)。单因素分析显示,与无ε4等位基因的患者相比,慢性脊髓压迫且携带纯合或杂合ε4等位基因的患者更易发生CSM(65.0%对35.0%,P<0.008;OR 3.5;95%CI 1.3 - 9.8)。在针对其他已知CSM危险因素进行调整的二元逻辑回归模型中,这种效应仍然显著。与不含ε4的模型相比,纳入纯合或杂合ε4等位基因变量后模型的拟合优度增加。
本研究支持以下假设,即APOEε4等位基因增加了慢性颈椎脊髓压迫患者发生CSM的风险;然而,需要更大规模的基于人群的前瞻性研究来明确回答这个问题。