Cesana Francesca, Nava Stefano, Menni Cristina, Boffi Lucia, Varrenti Marisa, Meani Paolo, Maloberti Alessandro, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
Department of Health Sciences, University of Milano-Bicocca , Milan , Italy.
Blood Press. 2013 Oct;22(5):302-6. doi: 10.3109/08037051.2013.765627. Epub 2013 Feb 27.
Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid-femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects.
The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing.
Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640.
These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.
有证据表明，动脉僵硬度是心血管疾病和全因死亡率的独立预测因子，且具有遗传成分。9p21区域与冠心病易感性增加有关。然而，位于9号染色体上的基因是否也能调节动脉僵硬度，这一点很大程度上尚不清楚。我们在821名高血压患者队列中，评估了通过Complior方法测量的9p单核苷酸多态性（SNP）对颈股脉搏波速度（C-F PWV）的影响。
在Illumina BeadXpress Reader平台上，使用定制设计的384重VeraCode金标准基因分型检测法筛选选定的标签SNP。使用PLINK进行关联分析，将C-F PWV视为定量性状（采用线性回归并假定为加性模型），并对性别、年龄、收缩压和体重指数（BMI）进行校正。我们使用错误发现率（FDR）来处理多重检验问题。
尽管在进行多重检验校正后，384个SNP均无显著意义，这可能是由于研究人群样本量较小，但rs300622和rs2381640与C-F PWV存在关联趋势。
这些数据表明，位于9号染色体上的SNP可能影响动脉僵硬度。需要进一步研究以在更大样本上证实我们的发现，并确定当前结果的生理病理联系。
