载脂蛋白B编码基因突变与冠心病发病风险及传统危险因素交互作用
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Study on the interaction between apolipoprotein B gene mutation and coronary heart disease risk and traditional risk factors
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    目的 探讨载脂蛋白B(APOB)编码基因突变与冠心病发病风险及传统危险因素的交互作用。方法 回顾性选取我院2010年1月~2016年1月收治既往未接受降脂治疗冠心病患者和非冠心病患者各386例,均行APOB编码基因R532W位点突变检测,分析各基因型患者血脂水平,分析此位点突变与冠心病发病相关性,同时评估其与冠心病危险因素在疾病发生过程中交互作用。结果 冠心病组患者高血压比例、糖尿病比例、吸烟比例、TC、LDLC、Apo B及FBG水平均显著高于非冠心病组(P<0.05);同时冠心病组收缩压、舒张压、HDLC、Apo AI及Apo AI/Apo B水平均显著低于非冠心病组(P<0.05);总纳入人群中AA型患者TC水平显著低于GA型(P<0.05);冠心病组AA型、GG型及GA型患者血脂指标水平比较差异无统计学意义(P>0.05);非冠心病组AA型患者TC水平显著低于GA型(P<0.05);非冠心病组和冠心病组患者POB编码基因R532W位点基因型分布频率比较差异有显著性(P<0.05);同时冠心病组最小等位基因A分布频率显著低于非冠心病组(P<0.05);显性遗传模型下,等位基因A携带者冠心病发病风险较未携带者降低29%(P<0.05);校正混杂因素后,等位基因A携带者冠心病发病风险较未携带者降低33%(P<0.05);隐性遗传模型和加性遗传模型下R532W位点突变与冠心病发病风险间无相关性(P>0.05);交互作用评价结果显示,APOB编码基因R532W位点突变和原发性高血压、吸烟史在冠心病发病过程中具有正相加交互效应(P<0.05),而与糖尿病具有负相加交互效应(P<0.05)。结论 既往未接受降脂治疗人群APOB编码基因R532W位点突变与TC水平密切相关,并能够在一定程度上降低远期冠心病发生风险;同时此位点突变与高血压、吸烟间可形成正相加交互,而与糖尿病则存在负相加交互。

    Abstract:

    Objective To investigate the interaction between apolipoprotein B gene mutation and attack risk of coronary heart disease and traditional risk factors. Methods Clinical data of 386 cases of coronary heart disease and 386 cases with noncoronary heart disease treated with no lipidlowering therapy were chosen in the period from January 2010 to January 2016. R532W mutation of ApoB coding gene was detected in all patients. The blood lipid level of different kinds of genotype was analyzed. The correlation between R532W mutation and coronary heart disease were analyzed and the interaction between this mutation and risk factors of coronary heart disease were evaluated. Results The proportion of hypertension, diabetes, smoking, TC, LDLC, apo B and FBG of CHD group were significantly higher than that of nonCHD group(P<0.05). The levels of SBP, DBP, HDLC, Apo AI and Apo AI/Apo B of CHD group were significantly lower than that of nonCHD group(P<0.05). The TC levels of patients with AA type were significantly lower than that of GA type(P<0.05). There was no significant difference in serum lipid levels among CHD patients with AA type, GG type and GA type(P<0.05). The TC levels of nonCHD patients with AA type were significantly lower than that of GA type(P<0.05). There were significant differences in the genotype distribution of R532W in POB coding gene between non CHD group and CHD group (P<0.05). The minimum allele A distribution frequency of CHD group were significantly lower than nonCHD group(P<0.05). In the dominant genetic model, the risk of coronary heart disease in allele A carriers were decreased for 29% lower than non carriers (P<0.05). After adjustment for confounding factors, the risk of coronary heart disease in allele A carriers were decreased for 33% lower than non carriers(P<0.05). There was no correlation between R532W mutation and the risk of coronary heart disease in recessive genetic model and additive genetic model(P>0.05). The results of interaction evaluation showed that R532W mutation in APOB coding gene and the history of hypertension and smoking possess positive additive interaction effect in the pathogenesis of coronary heart disease(P<0.05) and R532W mutation in APOB coding gene and diabetes possess negative additive interaction effect in the pathogenesis of coronary heart disease(P<0.05). Conclusion The mutation of R532W locus in APOB coding gene of people without lipidlowering therapy before is closely related to TC levels and can reduce the risk of longterm coronary heart disease to a certain extent. The mutation can form positive additive interaction with hypertension and smoking, while form negative additive interaction with diabetes.

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  • 在线发布日期: 2020-10-22
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