Feng Wei, Sun Lin, Qu Xiu-Fen
Pharmazie. 2017 Jan 10;72(1):17-21. doi: 10.1691/ph.2017.6752.
The renin-angiotensin system (RAS) is thought to play an important role in atrial fibrillation (AF). The RAS contains the ACE/AngII/AGTR1 axis and the ACE2/Ang(1-7)/MAS axis, which restrict each other via mutual antagonism and regulate myocardial hypertrophy, fibrosis and remodelling. The aim of our study was to investigate the association between single nucleotide polymorphisms (SNPs) in angiotensin-II type-1 receptor (AGTR1) and angiotensin-converting enzyme 2 (ACE2) and structural AF in a Chinese Han population. The SNPs (rs1492100, rs1492099, rs1492097, rs3772616) in AGTR1 and the SNP rs6632677 in ACE2 were compared in 300 structural AF patients (67.61±12.56 years) and 300 controls (66.08±12.47 years). The genotype frequencies of SNP rs1492099 in AGTR1 in the structural AF cohort vs controls were as follows: GG, 72.7 vs 83.0%; AG 26.0 vs 16.3%; AA 1.3 vs 0.7% (P=0.009). The frequency of the minor allele of SNP rs1492099 in AGTR1 was 14.2% in the structural AF group compared with 8.8% in the controls (t=0.004; odds ratio [OR], 1.727; 95% confidence interval [CI]: 1.154-2.487). In addition, the genotype frequencies of SNP rs6632677 in ACE2 in the structural AF male patients vs male controls were as follows: GG, 70.5 vs 83.1%; CG 26.3 vs 15.6%; and CC 3.2 vs 1.3% (P=0.029). The frequency of the minor allele of SNP rs6632677 in ACE2 was 16.3% in structural AF male patients compared with 9.1% in male controls (P=0.008; OR, 1.954; 95%CI: 1.196-3.192). Furthermore, we found an interaction between the SNP rs6632677 in ACE2 and the SNPs (rs1492100/rs1492099/rs3772616) in AGTR1 in structural AF patients by the multifactor dimensionality reduction (MDR) method. The results indicate that polymorphism rs1492099 in the AGTR1 gene is associated with structural AF in a Chinese Han population. It was hypothesized that the ACE2 gene, which maps to the X chromosome, may be correlated with the risk of structural AF in a Chinese Han male population. Furthermore, we found an interaction between ACE2 and AGTR1 in structural AF patients in a Chinese Han population.
肾素-血管紧张素系统（RAS）被认为在心房颤动（AF）中起重要作用。RAS包含ACE/AngII/AGTR1轴和ACE2/Ang(1-7)/MAS轴，它们通过相互拮抗作用相互制约，并调节心肌肥大、纤维化和重构。我们研究的目的是在中国汉族人群中调查血管紧张素II 1型受体（AGTR1）和血管紧张素转换酶2（ACE2）中的单核苷酸多态性（SNP）与结构性AF之间的关联。在300例结构性AF患者（67.61±12.56岁）和300例对照者（66.08±12.47岁）中比较了AGTR1中的SNP（rs1492100、rs1492099、rs1492097、rs3772616）和ACE2中的SNP rs6632677。结构性AF队列与对照者中AGTR里SNP rs1492099的基因型频率如下：GG，分别为72.7%和83.0%；AG，分别为26.0%和16.3%；AA，分别为1.3%和0.7%（P=0.009）。结构性AF组中AGTR1里SNP rs1492099的次要等位基因频率为14.2%，而对照组为8.8%（t=0.004；优势比[OR]，1.727；95%置信区间[CI]：1.154-2.487）。此外，结构性AF男性患者与男性对照者中ACE2里SNP rs6632677的基因型频率如下：GG，分别为70.5%和83.1%；CG，分别为26.3%和15.6%；CC，分别为3.2%和1.3%（P=0.029）。结构性AF男性患者中ACE2里SNP rs6632677的次要等位基因频率为16.3%，而男性对照者为9.1%（P=0.008；OR，1.954；95%CI：1.196-3.192）。此外，通过多因素降维（MDR）方法，我们发现结构性AF患者中ACE2里的SNP rs6632677与AGTR1中的SNP（rs1492100/rs1492099/rs3772616）之间存在相互作用。结果表明，AGTR1基因中的多态性rs1492099与中国汉族人群中的结构性AF相关。据推测，定位于X染色体的ACE2基因可能与中国汉族男性人群中结构性AF的风险相关。此外，我们发现中国汉族人群中结构性AF患者的ACE2和AGTR1之间存在相互作用。
