Vogiatzi Konstantina, Voudris Vassilis, Apostolakis Stavros, Kochiadakis Georgios E, Thomopoulou Sofia, Zaravinos Apostolos, Spandidos Demetrios A
Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Creece.
Thromb Res. 2009 May;124(1):84-9. doi: 10.1016/j.thromres.2008.12.043. Epub 2009 Feb 7.
Regulated on activation, normal T cell expressed and secreted (RANTES) gene promoter is a regulatory region and a site of notable genetic diversity. In order to explore a possible interaction between RANTES promoter genetic diversity and susceptibility to coronary artery disease (CAD) and in stent restenosis (ISR), we initially sequenced a locus extending from -516 to 40 covering the entire region of the RANTES promoter in 100 subjects randomly selected from our cohort. Four single nucleotide polymorphisms (SNPs) were identified: -403G/A, -256G/A, -109C/T and -28C/G. The frequency of the -109C/T and -256G/A variations was <0.01, and was considered to be of limited significance. The frequency of the -403G/A and -28C/G polymorphisms was evaluated in the entire sample, which consisted of 118 patients subjected to percutaneous coronary intervention (PCI) without ISR on angiographic re-evaluation (no IRS group), 74 CAD patients with ISR on angiographic re-evaluation (IRS group) and 146 controls without angiographic evidence of CAD (no CAD group). No association was established between the RANTES promoter genotype and ISR. A genotype-phenotype interaction was observed between the -403G/A polymorphism and CAD. The -403A homozygotes were significantly more common in the CAD group than in the controls. The severity of CAD among case subjects, expressed as the mean number of diseased vessels, was significantly higher among -403A homozygotes as compared to wild-type homozygotes and heterozygotes. In conclusion, the RANTES -403A allele was associated with the presence and severity of CAD independently of conventional cardiovascular risk factors. The RANTES promoter genotype did not influence susceptibility to ISR in patients subjected to PCI.
调节激活正常T细胞表达和分泌因子（RANTES）基因启动子是一个调控区域，也是显著遗传多样性的位点。为了探究RANTES启动子遗传多样性与冠状动脉疾病（CAD）及支架内再狭窄（ISR）易感性之间可能存在的相互作用，我们首先在从我们的队列中随机选取的100名受试者中，对一个从-516延伸至40的位点进行测序，该位点覆盖RANTES启动子的整个区域。鉴定出四个单核苷酸多态性（SNP）：-403G/A、-256G/A、-109C/T和-28C/G。-109C/T和-256G/A变异的频率<0.01，被认为意义有限。在整个样本中评估了-403G/A和-28C/G多态性，该样本包括118例经皮冠状动脉介入治疗（PCI）且血管造影复查无ISR的患者（无IRS组）、74例血管造影复查有ISR的CAD患者（IRS组）以及146例无CAD血管造影证据的对照者（无CAD组）。未发现RANTES启动子基因型与ISR之间存在关联。观察到-403G/A多态性与CAD之间存在基因型-表型相互作用。-403A纯合子在CAD组中比在对照组中显著更常见。病例受试者中CAD的严重程度，以病变血管的平均数表示，-403A纯合子比野生型纯合子和杂合子显著更高。总之，RANTES -403A等位基因与CAD的存在和严重程度相关，独立于传统心血管危险因素。RANTES启动子基因型不影响接受PCI患者对ISR的易感性。
