Wang Xu, Nie Yali, Ning Shuwei, Shi Yong, Zhao Yujie, Niu Siquan, Guo Chengxian, Meng Xiangguang, Yuan Yiqiang
Department of Cardiology, Henan Cardiovascular Hospital, Affiliated to Southern Medical University, Zhengzhou 450016, China.
Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450000, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Jun 28;43(6):594-603. doi: 10.11817/j.issn.1672-7347.2018.06.004.
To determine the correlations of single nucleotide polymorphisms (SNPs) with atrial fibrillation (AF) in the Chinese Han population from the central plains. Methods: A total of 168 hospitalized patients, including 56 AF and 112 controls, were recruited in this case-control study. The clinical data were obtained from the medical records. All 5 SNPs, rs337711 in KCNN2, rs11264280 near KCNN3, rs17042171 near PITX2, rs6771157 and rs6795970 in SCN10A, were genotyped using amplification refractory mutation system-polymerase chain reaction or direct sequencing. The χ2 test was used to compare categorical variables and preliminarily examine correlations between the genotype frequencies and AF. Subsequently, a logistic regression model was constructed to determine the associations between the SNPs and AF based on the above screened results. Odds ratios (ORs) and 95% confidence interval (CI) were calculated to assess the strength of the correlations. Moreover, we downloaded the genotype data from the HapMap Project for linkage disequilibrium analysis of rs17042171. Results: AF patients were likely to be of older age and longer left atrial diameter and had more coronary artery disease and higher hypertension compared with the control group (P<0.05). Among the 5 SNPs, the frequency distribution of genotype AA for rs17042171 was significantly different between the AF and control groups (P<0.05). After adjusting for several covariates, there was still a high risk ratio in patients with the AA genotype compared with the AC+CC genotype (OR: 5.591, 95%CI 2.176 to 14.365, P-B<0.008). Similarly, stratification analysis on the AA genotype demonstrated significant differences between rs17042171 and persistent AF. However, there were not significant correlations between AF and the control groups for the other 4 SNPs (P<0.05). Conclusion: Rs17042171, near PITX2 on chromosome 4q25, is associated with AF susceptibility in the Chinese Han population from the central plains, suggesting that this SNP can provide a new strategy for clinical diagnosis in AF patients.
为确定中国中原地区汉族人群中，单核苷酸多态性（SNP）与心房颤动（AF）之间的相关性。
本病例对照研究共纳入168例住院患者，其中包括56例AF患者和112例对照。临床资料来自病历。采用扩增阻滞突变系统-聚合酶链反应或直接测序法对KCNN2基因中的rs337711、KCNN3基因附近的rs11264280、PITX2基因附近的rs17042171、SCN10A基因中的rs6771157和rs6795970这5个SNP进行基因分型。采用χ2检验比较分类变量，并初步检验基因型频率与AF之间的相关性。随后，根据上述筛选结果构建逻辑回归模型，以确定SNP与AF之间的关联。计算比值比（OR）和95%置信区间（CI），以评估相关性强度。此外，我们从HapMap计划下载了基因型数据，用于rs17042171的连锁不平衡分析。
与对照组相比，AF患者年龄更大、左心房直径更长，冠心病和高血压的发生率更高（P<0.05）。在这5个SNP中，rs17042171的基因型AA频率分布在AF组和对照组之间存在显著差异（P<0.05）。在调整了几个协变量后，与AC+CC基因型相比，AA基因型患者的风险比仍然很高（OR：5.591，95%CI 2.176至14.365，P<0.008）。同样，对AA基因型的分层分析表明，rs17042171与持续性AF之间存在显著差异。然而，其他4个SNP在AF组和对照组之间没有显著相关性（P<0.05）。
位于4号染色体q25上PITX2基因附近的rs17042171与中国中原地区汉族人群的AF易感性相关，表明该SNP可为AF患者的临床诊断提供新策略。
