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Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population

机译:ZFHX3基因中的SNP rs2106261与中国汉族GeneID人群的房颤显着相关

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Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P = 0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR = 1.32), and genotypic frequencies assuming either an additive or recessive model (OR = 1.29, P = 0.001 and OR = 1.77, P = 0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR = 1.50, P = 0.001 for allelic association; OR = 1.45, P = 0.001 for an additive model; OR = 2.24, P = 0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.
机译:心房颤动(AF)是临床上最常见的心律失常,占所有卒中的15%。最近的全基因组关联研究(GWAS)确定了两个单核苷酸多态性(SNP),分别是ZFHX3(锌指同源盒3基因)中的rs2106261和rs7193343,以及KCNN3中的rs13376333(编码一个钾中/小电导钙激活通道,亚家族N,成员3)在欧洲血统的多个人群中均显示出与房颤的显着相关性。在这里,我们研究了由650名AF患者和1,447名非AF对照组成的中国汉族GeneID队列,以测试GWAS在ZFHX3 / KCNN3和AF上的发现是否可以扩展到其他种族。 ZFHX3中的rs7193343和KCNN3中的rs13376333未检测到显着关联。但是,在两个等位基因频率(校正年龄,性别,高血压,冠状动脉疾病和糖尿病的协变量后,P = 0.001; OR = 1.32)和基因型之间,在ZFHX3的rs2106261和GeneID人群的AF之间发现了显着关联。频率假设是加性模型或隐性模型(分别为OR = 1.29,P = 0.001和OR = 1.77,P = 0.00018)。仅分析孤立的AF病例时,关联仍然很显着(对于等位基因关联,OR = 1.50,P = 0.001;对于加性模型,OR = 1.45,P = 0.001;对于隐性模型,OR = 2.24,P = 0.000043)。我们的结果表明,ZFHX3中的rs2106261在中国汉族人群中具有很大的房颤风险。这项研究将ZFHX3和AF之间的联系扩展到了非欧洲血统人群,并提供了16q22 AF基因座的跨种族敏感性的第一个证据。

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