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Title: [Interaction between APOB gene polymorphism and risk factors in coronary heart disease patients without lipid-lowering treatment].
Author: Pu T, Yu HY, Xu M, Zhang Y, Yan H, Sun LJ, Xu WX, Zhang YY, Gao W.
Journal: Zhonghua Xin Xue Guan Bing Za Zhi; 2017 May 24; 45(5):386-392. PubMed ID: 28511322.
Abstract:
Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD. 目的： 探讨未接受降脂治疗的冠心病患者APOB基因R532W位点多态性与冠心病发病风险的相关性，并分析该位点变异与冠心病危险因素在冠心病发病中的交互作用。 方法： 选取2006年1月至2013年1月于北京大学第三医院经冠状动脉造影证实1支或以上冠状动脉主要分支管腔狭窄≥50%，且临床诊断为冠心病的患者作为冠心病组(771例)，另选取同期与冠心病组患者年龄、性别匹配，冠状动脉造影或CT血管造影(CTA)未见冠状动脉主要分支管腔狭窄≥50%，且临床症状、心电图等检查除外冠心病者作为对照组(772例)。所有入选者均为中国北方汉族人群，既往均未接受任何降脂治疗。检测入选者的血脂指标。采用HumanExome BeadChip对入选者进行R532W基因分型测定。比较不同基因型患者间的血脂水平，并在显性(GA＋AA比GG)、隐性(AA比GG＋GA)和加性(AA比GA比GG)遗传模型下分析该位点变异与冠心病发病风险的关系，探讨该位点与冠心病危险因素在冠心病发病中的交互作用。 结果： (1)APOB基因R532W多态性与血脂水平的关系：在总体入选者中，AA基因型患者TC水平较GA基因型患者低(P<0.05)，而AA与GG基因型，GA与GG基因型患者间TC水平差异则均无统计学意义，3种基因型的患者间其他血脂指标差异均无统计学意义。冠心病组3种基因型的患者间各血脂指标差异均无统计学意义。对照组中AA基因型患者TC水平较GA基因型低(P<0.05)，而AA与GG基因型，GA与GG基因型患者间TC水平差异则均无统计学意义，3种基因型的患者间其他血脂指标差异均无统计学意义。(2)APOB基因R532W的等位基因和基因型频率分布的比较：R532W位点的GG、GA、AA 3种基因型在冠心病组患者中的频率分别为80.7%、18.2%和1.2%，在对照组患者中分别为74.6%、23.8%和1.6%，两组间频率分布差异有统计学意义(P<0.05)。R532W最小等位基因频率为11.9%，且最小等位基因A的频率在冠心病组患者中低于对照组(10.2%比13.5%，P<0.05)。(3)APOB基因R532W与冠心病发病风险的logistic回归分析结果：在显性遗传模型下(GA＋AA比GG)，A等位基因携带者较未携带者冠心病发病风险约低30%(OR＝0.704, 95%CI 0.553～0.869, P＝0.004)；进一步校正性别、年龄、高血压、糖尿病和吸烟等混杂因素后，A等位基因携带者较未携带者冠心病发病风险低(OR＝0.653, 95%CI 0.502～0.849, P＝0.001)。而在隐性遗传模型下(AA比GG＋GA )和加性遗传模型下(AA比GA比GG)，无论是否校正混杂因素，均未见R532W的多态性与冠心病发病风险相关(P>0.05)。(4)APOB基因R532W与危险因素在冠心病发病中的交互作用：R532W位点变异与高血压、吸烟在冠心病发病中存在正相加交互作用，交互作用强度分别为1.453、1.077。而APOB基因R532W位点变异与糖尿病在冠心病发病中存在负相加交互作用，交互作用强度为0.553。 结论： APOB基因R532W位点变异与中国北方汉族人群TC水平相关，其在一定程度上可降低未接受降脂治疗患者的冠心病发病风险，且与高血压、吸烟在冠心病发生中存在正相加交互作用，与糖尿病存在负相加交互作用。.

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