高脂血症患者APOB/CⅢ/E基因多态性交互作用的研究

Study on gene-gene interaction of gene loci of apolipoprotein B/CⅢ/E polymorphism in patients with essential hyperlipidemia

目的探讨原发性高脂血症载脂蛋白(Apo)B、CⅢ、E基因中ApoB MspI、ApoB XbaI、ApoB EcorI、ApoCI-II3175、ApoCIII3206、ApoE112/158等7个位点基因多态性间的交互作用。方法采用病例-对照相关性研究策略,选择昆明地区汉族作为研究对象,用基因芯片检测技术,对91例高脂血症患者及76例健康对照者进行ApoB MspI、ApoBXbaI、ApoB EcorI、ApoCⅢ3175、ApoCIII3206、ApoE112/158等6个位点基因多态性进行检测。用比值比(odd ratio,OR)估计相对危险度。用MDR分析多基因相互作用。结果用MDR分析法,对昆明地区汉族高脂血症患者上述6个位点基因型多态性的基因-基因交互作用进行了分析,发现两位点MspI-E112/158、三位点MspI-CIII3206-E112/158和四位点MspI-XbaI-CIII3206-E112/158这三种模型均具有统计学意义(P<0.001),但三位点MspI-CⅢ3206-E112/15模型的交叉验证一致性系数最大(10/10)为最佳模型,该模型包含了位点ApoB MspI、ApoCⅢ3206和ApoE112/158位点,提示这三个基因位点之间可能存在基因-基因交互作用。该模型的Odd Ratio为14.870(95%CI:1.305-169.43)。结论发现昆明地区汉族人群7个高脂血症候选基因位点中,MspI-CIII3206-E112/158三个基因多态性之间可能存在基因-基因交互作用。

Objective To investigate the gene - gene interaction between polymorphism of seven candidate gene loci （including ApoB MspI, ApoB XbaI, ApoB EcorI, ApoCIII3175, ApoCIII3206 andApoE112/158 ） and essential hyperlipidemia. Methods The strategy is ease - control association study. Ninety one patients with essential hyperlipidemia and 76 healthy controls were Han nationality in Kunming Area . The genotypes of ApoB MspI, ApoB XbaI, ApoB EcorI, ApoCIII3175, ApoCIII3206 and ApoE112/158 were detected with DNA microarray. The relative risk of hyperlipidemia was estimated by Odd Ratio. The gene - gene interaction of them was detected with multifactor dimensionality reduction （MDR） method. Results MDR analysis displays that there are three significant models of gene - gene interaction among seven candidate loci. They are MspI - E112/158, MspI - CIIB206 - E112/158, and MspI - XbaI - CIII3206 - E112/158. However, MspI - CIIB206 - E112/158 is the best one of them. The Odd Ratio of the best model is 14. 870 （95 % CI ： 1. 305 - 169.43 ）. Conclusion The potential gene - gene interaction exists among MspI, CIIB206 and ApoE112/158 in patients with essential hyperlipidemia.