[Rs17042171 at chromosome 4q25 is associated with atrial fibrillation in the Chinese Han population from the central plains]

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.
[Article in Chinese]

Abstract

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.

目的:确定中国中原地区汉族人群中单核苷酸多态性位点(SNPs)rs337711,rs11264280,rs17042171,rs6771157和rs6795970与心房颤动(以下简称房颤)的相关性。方法:研究共纳入168例患者,包括房颤组(56例)和对照组(112例)。采用突变扩增系统-聚合酶链式反应或直接测序法对上述5个SNPs进行基因分型。构建4种经典遗传模型以确定SNPs与房颤的关联性。结果:房颤组与对照组相比具有更大的年龄和左房内径及频发的冠心病和高血压(P<0.05)。rs17042171基因型AA的频率分布在房颤组和对照组间差异有统计学意义(P<0.05),在校正几个临床因素之后两组间差异仍有统计学意义(OR:5.591,95%CI:2.176~14.365,P-B<0.008)。其他4个SNPs的基因型分布在房颤组和对照组之间差异无统计学意义(P>0.05)。结论:染色体4q25区域的rs17042171与中国中原地区汉族人群的房颤易感性相关,该SNP可能为房颤患者临床诊断提供新的策略。.

MeSH terms

  • Age Factors
  • Asian People
  • Atrial Fibrillation / ethnology
  • Atrial Fibrillation / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • China / ethnology
  • Chromosomes, Human, 4-5
  • Genetic Predisposition to Disease
  • Genotype
  • Geography
  • Homeobox Protein PITX2
  • Homeodomain Proteins / genetics
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • NAV1.8 Voltage-Gated Sodium Channel / genetics
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Transcription Factors / genetics

Substances

  • Homeodomain Proteins
  • KCNN2 protein, human
  • KCNN3 protein, human
  • NAV1.8 Voltage-Gated Sodium Channel
  • SCN10A protein, human
  • Small-Conductance Calcium-Activated Potassium Channels
  • Transcription Factors