Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2012;7(8):e42401. doi: 10.1371/journal.pone.0042401. Epub 2012 Aug 3.
Coronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.
METHODOLOGY/PRINCIPAL FINDINGS: Candidate genes were selected using a MEDLINE search including the terms 'genetic polymorphism' and 'coronary restenosis'. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes.
Despite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.
尽管医学取得了所有进步，经皮冠状动脉介入治疗后的冠状动脉再狭窄仍然是一个重大问题。揭示导致再狭窄发展的机制仍然具有挑战性。许多研究已经确定了与再狭窄相关的遗传标记物，但报告标记物的一致性复制很少。本研究的目的是分析先前文献中报道的与再狭窄相关的候选基因在 GENetic DEterminants of Restenosis (GENDER) 数据库中的联合效应。
方法/主要发现：使用 MEDLINE 搜索，包括“遗传多态性”和“冠状动脉再狭窄”这两个术语，选择候选基因。最终的集合包括 36 个基因。随后，在 GENDER 中使用 PLINK 中的基于集合的分析分析这些基因的基因组区域中的所有单核苷酸多态性（SNP）。GENDER 数据库包含 295 例再狭窄病例和 571 例匹配对照的 2,571,586 个 SNP 的基因型数据。包括所有 36 个文献报道基因的集合确实与再狭窄显著相关，在 GENDER 研究中 p = 0.024。对个别基因的后续分析表明，观察到的整个集合的关联是由 36 个基因中的 6 个决定的。
尽管在个体候选基因研究方面存在明显的不一致，但这是第一项表明所有这些基因的联合效应确实与再狭窄相关的研究。
