O'Shaughnessy Kevin M, McEniery Carmel M, Cockcroft John R, Wilkinson Ian B
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
J Hypertens. 2006 Mar;24(3):499-502. doi: 10.1097/01.hjh.0000209986.74477.18.
Arterial stiffness is an independent determinant of cardiovascular risk, and there is evidence that it has a strong genetic component. Fibrillin-1 (FBN-1) is the disease gene for Marfan's syndrome and an FBN-1 polymorphism has been associated with large artery stiffening and elevated pulse pressure (PP) in patients with cardiovascular disease. The aim of this study was to investigate the possible influence of the common FBN-1 genotypes on arterial stiffness in a large cohort of healthy individuals.
A total of 742 individuals free from cardiovascular disease or risk factors were studied. Aortic pulse wave velocity (PWV) and augmentation index (AIx), blood pressure, lipids and glucose were assessed. Genomic DNA was extracted, and genotyping for the FBN-1 variable nucleotide tandem repeat (VNTR) was performed using a CEQ 8000 sequencer.
The mean age (+/- SEM) of the cohort was 49 +/- 1 years. The three common VNTR genotypes accounted for 87.1% of the population frequency. Their frequencies were: 52.3%, 2-2; 16.3%, 2-3; 18.5% 2-4. There were no significant differences in the blood pressure, AIx, PWV, lipids or body mass index among the common genotypes. Moreover, the FBN-1 genotype was not associated with either aortic PWV or other measures of stiffness after correction for other confounding factors.
These data do not support the hypothesis that aortic PWV or PP are influenced by the FBN-1 VNTR genotype. Although we cannot exclude small effects, this negative finding also suggests that there is not a major allele for stiffness or blood pressure in apparently healthy individuals linked to this VNTR.
动脉僵硬度是心血管风险的独立决定因素，且有证据表明其具有很强的遗传成分。原纤维蛋白-1（FBN-1）是马方综合征的致病基因，一种FBN-1多态性与心血管疾病患者的大动脉僵硬度增加和脉压（PP）升高有关。本研究的目的是调查常见FBN-1基因型对一大群健康个体动脉僵硬度的可能影响。
共研究了742名无心血管疾病或风险因素的个体。评估了主动脉脉搏波速度（PWV）和增强指数（AIx）、血压、血脂和血糖。提取基因组DNA，并使用CEQ 8000测序仪对FBN-1可变核苷酸串联重复序列（VNTR）进行基因分型。
该队列的平均年龄（±标准误）为49±1岁。三种常见的VNTR基因型占人群频率的87.1%。它们的频率分别为：52.3%，2-2；16.3%，2-3；18.5%，2-4。常见基因型之间在血压、AIx、PWV、血脂或体重指数方面无显著差异。此外，在校正其他混杂因素后，FBN-1基因型与主动脉PWV或其他僵硬度指标均无关联。
这些数据不支持主动脉PWV或PP受FBN-1 VNTR基因型影响的假设。虽然我们不能排除微小影响，但这一阴性结果也表明，在与该VNTR相关的明显健康个体中，不存在影响僵硬度或血压的主要等位基因。
