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中国汉族人群中PPARG与CYP1A1基因在冠状动脉疾病上的基因-基因相互作用。

Gene-gene interaction between PPARG and CYP1A1 gene on coronary artery disease in the Chinese Han Population.

作者信息

Zhang Xiaojiang, Lv Shuzheng, Guo Chengjun, Shi Conghong, Chi Yunpeng, Zhao Lin, Wang Guozhong, Wang Zhisheng

机构信息

Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China.

Baotou Fourth Hospital, Baotou, Inner Mongolia, 014030, China.

出版信息

Oncotarget. 2017 May 23;8(21):34398-34404. doi: 10.18632/oncotarget.16186.

Abstract

AIMS

To observe the influence of the peroxisome proliferator-activator receptor-G (PPAR-G) gene and cytochrome P4501A1 (CYP1A1) single-nucleotide polymorphisms (SNPs), and interactions among several SNPs on coronary artery disease (CAD) risk.

METHODS

A total of 1106 participants (including 583 males and 523 females) including 550 CAD patients and 556 control subjects were recruited in this study, and the mean age for these participants was 55.5 ± 11.8 years old. Logistic regression was used to observe association of SNP within PPARG and CYP1A1 with CAD risk and GMDR model was used to screen the best interaction combinations.

RESULTS

CAD susceptibility was higher in those with homozygous mutant of rs10865710, rs1805192 and rs4646903 than those with wild-type homozygotes, OR (95%CI) were 1.47 (1.15-1.92), 1.69 (1.27-2.09) and 1.72 (1.35-2.32), respectively. We also found a significant two-locus model involving rs1805192 and rs4646903 (p = 0.0107), and the cross-validation consistency of this locus model was 10 of 10, the testing accuracy of this model is 62.17%. Logistic regression shown that CAD risk was the highest in those with rs1805192- Pro/Ala or Ala/Ala and rs4646903- AG+GG genotype, and was lowest in those with rs1805192- Pro/ Pro and rs4646903- AA genotype, OR(95%CI) = 3.56 (1.91-5.42).

CONCLUSIONS

Polymorphism in rs10865710, rs1805192 and rs4646903 and interaction between rs1805192 and rs4646903 were related with increased CAD susceptibility.

摘要

目的

观察过氧化物酶体增殖物激活受体γ(PPAR-γ)基因和细胞色素P4501A1(CYP1A1)单核苷酸多态性(SNP),以及多个SNP之间的相互作用对冠心病(CAD)风险的影响。

方法

本研究共纳入1106名参与者(包括583名男性和523名女性),其中550例为CAD患者,556例为对照者,参与者的平均年龄为55.5±11.8岁。采用逻辑回归观察PPARG和CYP1A1内SNP与CAD风险的关联,并使用GMDR模型筛选最佳相互作用组合。

结果

rs10865710、rs1805192和rs4646903纯合突变者的CAD易感性高于野生型纯合子,OR(95%CI)分别为1.47(1.15-1.92)、1.69(1.27-2.09)和1.72(1.35-2.32)。我们还发现一个涉及rs1805192和rs4646903的显著两位点模型(p = 0.0107),该位点模型的交叉验证一致性为10/10,该模型的检验准确性为62.17%。逻辑回归显示,rs1805192为Pro/Ala或Ala/Ala且rs4646903为AG+GG基因型者的CAD风险最高,rs1805192为Pro/Pro且rs4646903为AA基因型者的CAD风险最低,OR(95%CI)=3.56(1.91-5.42)。

结论

rs10865710、rs1805192和rs4646903的多态性以及rs1805192与rs4646903之间的相互作用与CAD易感性增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1f/5470977/37b19112cba8/oncotarget-08-34398-g001.jpg

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