| 摘要: |
| 目的探讨花生四烯酸（AA）细胞色素P450酶（CYP）代谢通路基因多态性及基因-基因交互作用与脑梗死发病的相关性。方法选择经头颅CT和/或MRI检查确诊、起病72h内入院、首次发病的脑梗死患者300例为病例组，同期健康体检者298例为对照组。应用基质辅助激光解吸附电离飞行时间质谱法（MALDI-TOFMS）检测CYP2C8基因rs17110453、rs1934980，CYP2J2基因rs10889160，CYP4A11基因rs2269231、rs9333025和CYP4F2基因rs3093135的单核苷酸多态性（SNP），应用广义多因子降维法（GMDR）检测基因-基因交互作用。结果单基因分析发现，两组间6个基因位点的基因型分布差异均无统计学意义（均P＞0.05）。GMDR分析发现，rs17110453和rs9333025两个基因位点具有交互作用，最优模型为rs17110453和rs9333025两个基因位点联合作用模型，交叉检验一致性为10/10，符号检验为9（P=0.0112）；交互作用风险较大的组合依次为rs17110453CC+rs9333025GG、rs17110453CC+rs9333025GG/AG、rs17110453CC+rs9333025AG。多因素logistic回归分析发现调整年龄、高血压、糖尿病因素后，rs17110453和rs9333025的高风险交互变量与脑梗死发病风险相关（OR=2.96，95%CI：1.58~8.26，P=0.000）。结论rs17110453和rs9333025两基因位点联合交互作用可明显增加脑梗死发病的风险。 |
| 关键词: 花生四烯酸 细胞色素 P450 酶 单核苷酸多态性 脑梗死 相关性 |
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| Association of polymorphisms in arachidonic acid cytochrome P450 metabolic pathway genes with susceptibility of cerebral infarction |
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CHEN Yiming, YU Zezhen, ZHOU Qiang, LI Qiang, CHI Lifen, YI Xingyang
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the Third Affiliated Hospital of Wenzhou Medical University
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| Abstract: |
| Objective To investigate the association of single nucleotide polymorphisms (SNP) in arachidonic acid (AA) cytochrome P450 (CYP) pathway genes with the risk of cerebral infarction (CI). Methods Three hundred patients with CI and 298 health subjects were enrolled in the study. CYP2C8 rs17110453, CYP2C8 rs1934980, CYP2J2 rs10889160, CYP4A11 rs2269231, CYP4A11 rs9333025 and CYP4F2 rs3093135 genes SNP were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS) method. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. Results Single gene variant analysis found that there were no significant differences in genotype distributions between patients and controls. However, GMDR analysis showed a significant gene-gene interaction between rs17110453 and rs9333025 with a score of 10/10 for the cross-validation consistency and 9 for sign test (P=0.0112). Patients with combination of rs17110453CC+rs9333025GG, rs17110453CC+rs9333025GG/AG, rs17110453 CC+rs9333025AG had a significantly higher risk for CI. Logistic regression analysis showed that the high-risk interactive genotypes among rs17110453 and rs9333025 were independent risk factors of CI after adjustment for age, hypertension and diabetes mellitus factors (OR=2.96, 95% CI:1.58-8.26, P=0.000). Conclusion The interaction of two gene-loci rs17110453 and rs9333025 significantly increases the risk of CI. |
| Key words: Arachidonic acid Cytochrome P450 enzyme Single nucleotide polymorphism Cerebral infarction
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