与冠状动脉疾病相关的新发致心律失常性猝死风险增加的相关基因座。
Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease.
机构信息
The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
出版信息
PLoS One. 2013 Apr 4;8(4):e59905. doi: 10.1371/journal.pone.0059905. Print 2013.
BACKGROUND
Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).
METHODS AND FINDINGS
Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8), OR = 2.41).
CONCLUSIONS
Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.
背景
最近的全基因组关联研究（GWAS）已经确定了与心源性猝死（SCD）相关的新基因座。尽管取得了这一进展，但已鉴定的 DNA 变体仅占 SCD 总风险的相对较小部分，这表明还有其他基因座有待发现，这些基因座可能导致 SCD 易感性。本研究的目的是确定与冠心病（CAD）相关的 SCD 相关的新型 DNA 变异。
方法和发现
使用 MetaboChip 定制阵列，我们对来自俄勒冈州猝然意外死亡研究（Oregon-SUDS）的 948 例 SCD 病例（伴有基础 CAD）中的 119,117 个 SNP 进行了病例对照关联分析，这些病例来自俄勒冈州猝然意外死亡研究（Oregon-SUDS），以及来自威康信托基金会-病例对照研究协作组织（WTCCC）的 3,050 例 CAD 对照者。两个新确定的基因座在经过多次比较校正后与 SCD 风险增加显著相关：位于染色体 2 的 RAB3GAP1 基因中的 rs6730157（P=4.93×10(-12)，OR=1.60）和位于染色体 10 的 ZNF365 基因中的 rs2077316（P=3.64×10(-8)，OR=2.41）。
结论
我们的研究结果表明，RAB3GAP1 和 ZNF365 是 SCD 的相关候选基因，将有助于对 SCD 易感性的机制理解。
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