CYP4A11和载脂蛋白B、E基因多态性与原发性高血压患病风险的相关性
Association Analysis between Genetic Polymorphisms of CYP4A11, Apolipoprotein B and E Genes and Essential Hypertension Susceptibility
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摘要: 目的 探讨CYP4A11基因和载脂蛋白B、E基因 (Apo B、Apo E) 多态性与原发性高血压之间的相关性.方法 采用病例-对照的研究设计, 通过关联分析的研究方法, 严格按照标准选取2012年6月至2016年12月西安市第一医院收治的350例原发性高血压患者为原发性高血压组, 另选取350例于同时期在西安市第一医院行常规性检查的正常体检者为对照组, 采用Mass ARRAY方法对2组人群进行CYP4A11基因和Apo B、Apo E基因多态性检测, 用SPSS软件统计基因多态性与原发性高血压患病风险的相关性.结果 通过比较各位点的等位基因频率, 研究结果显示, 在等位基因模型下, CYP4A11基因上的rs1126742 (OR=1.45, 95%CI, 1.091.92, P=0.008) 、rs3890011 (OR=1.98, 95%CI, 1.061.85, P=0.001) 以及rs9332978 (OR=1.54, 95%CI, 1.271.91, P=0.004) 这3个多态性位点会显著增加原发性高血压的患病风险;Apo B基因上的XbaⅠ多态性与原发性高血压的患病风险相关 (OR=1.55, 95%CI, 1.152.55, P=0.001) , Apo B基因上的Eco RⅠ多态性与原发性高血压的患病风险不存在相关性 (P>0.05) ;Apo E基因ε4多态性与原发性高血压的患病风险相关 (OR=1.49, 95%CI, 1.092.35, P=0.012) , ε2、ε3多态性与原发性高血压的患病风险不存在相关性 (P>0.05) .通过比较各位点的基因型频率, CYP4A11基因rs9332978位点的GG基因型、rs1126742位点的TC与CC基因型以及rs3890011位点的CG与GG基因型均可增加原发性高血压的患病风险 (P<0.05) ;Apo B基因XbaⅠ多态性位点的X-X-基因型能显著增加原发性高血压的患病风险 (OR=2.45, 95%CI, 1.253.25, P=0.035) ;Apo E基因的E2/E4、E3/E4、E4/E4基因型均能显著增加原发性高血压的患病风险 (P<0.05) .引入遗传模型分析后, 研究结果显示, 在隐性模型下, rs9332978的最小等位基因A与增加原发性高血压患病风险具有相关性 (OR=1.61, 95%CI, 1.282.03, P=0.001) ;rs1126742的最小等位基因T在显性和隐性遗传模型下均与原发性高血压患病风险显著相关 (显性模型:OR=1.45, 95%CI, 1.091.82, P=0.008;隐性模型:OR=1.37, 95%CI, 1.112.16, P=0.004) .结论 CYP4A11 (rs9332978、rs1126742和rs3890011位点) 基因以及Apo B (XbaⅠ) 、Apo E基因多态性在原发性高血压的发生发展中起着至关重要的作用.Abstract: Objective To investigate the association between single nucleotide polymorphisms (SNPs) in CYP4A11 and Apo B、 Apo E genesandthe risk of essential hypertension. Me thods By means of correlation analysis, this case-controlled study included a total of 350 essential hypertension patients admitted in the first Hospital of Xi'an from June 2012 to December 2016, and another 350 cases with matched ages and sexes enrolled for routine check-ups as the healthy control group. The genotypes of CYP4A11 and Apo B、 Apo E genes were determined by Mass ARRAY method. SPSS 21.0 software was used to determine the correlation between SNPs and the risk of primary hypertension.Re s ults Comparing the allele frequencies of SNPs, we found rs1126742 (OR=1.45, 95 % CI, 1.09-1.92, P =0.008) 、 rs3890011 (OR=1.98, 95 % CI, 1.06-1.85, P =0.001) and rs9332978 (OR=1.54, 95 % CI, 1.27-1.91, P=0.004) on CYP4A11 were significantly associated with an increased risk of essential hypertension; Xba Ⅰ polymorphism in Apo B gene was associated with essential hypertension risks (OR=1.55, 95 % CI, 1.15-2.55, P=0.001) ;ε4 in Apo E gene was also found associated with essential hypertension risks (OR=1.49, 95 % CI, 1.09-2.35, P =0.012) , while ε2 andε3 not associated.Comparing the genotype frequencies of SNPs, we found the GG genotype of rs9332978, TC and CC genotype of rs1126742, CG and GG genotypes of rs3890011 were associated with increased risks of essential hypertension (P <0.05) .The X-X-genotype of Xba Ⅰ in Apo B gene were associated with increased risks of essential hypertension (OR=2.45, 95 % CI, 1.25-3.25, P = 0.035) . The E2/E4、E3/E4、E4/E4 genotype of Apo E were associated with increased risks of essential hypertension (P<0.05) .In the genetic model analysis, we found that the minor allele "A" of rs9332978 was associated with an increased risk of essential hypertension under dominant model (P <0.05) . The minor allele "T" of rs1126742 was associated with increased risks essential hypertension under dominant and recessive models (P<0.05) . Conclus ion Gene polymorphisms of CYP4A11、Apo B and Apo E play an important role in the occurrence and development of essential hypertension.
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Key words:
- Essential hypertension /
- CYP4A11 /
- ApoB /
- ApoE /
- Ggene polymorphisms
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