van Moorsel Dirk, Henry Ronald M, Schaper Nicolaas C, van Greevenbroek Marleen M, van Rossum Elisabeth F, 't Hart Leen M, Schalkwijk Casper G, van der Kallen Carla J, Dekker Jacqueline M, Stehouwer Coen D, Havekes Bas
Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Human Biology and Human Movement Sciences, Maastricht University Medical Center, Maastricht, The Netherlands.
Am J Hypertens. 2017 Mar 1;30(3):286-294. doi: 10.1093/ajh/hpw196.
Chronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.
We conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 ± 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.
We identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 ± 5.37 vs. 12.87 ± 5.55 10-3/kPa [mean ± SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.
Even though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.
长期糖皮质激素过量与动脉僵硬和心脏功能障碍有关。BclI糖皮质激素受体（GR）多态性会增加GR敏感性，并与较高的体重指数（BMI）以及一些心血管疾病（CVD）指标相关。目前尚不清楚BclI是否会影响动脉僵硬和心脏功能障碍。因此，本研究的目的是调查BclI多态性与动脉僵硬以及心脏结构和功能之间的关联。
我们进行了一项观察性队列研究，合并了两项旨在调查CVD遗传和代谢决定因素的队列研究。我们对来自霍伦研究和马斯特里赫特糖尿病与动脉粥样硬化队列（CODAM）研究的1124名个体（年龄：64.7±8.5岁）进行了BclI基因分型。测定了颈动脉（霍伦和CODAM研究）、肱动脉和股动脉的几个动脉僵硬指数以及颈动脉-股动脉脉搏波速度（仅霍伦研究）。此外，在霍伦研究中，我们测定了心脏结构和功能的几个变量。
我们鉴定出BclI多态性的155名纯合携带者（GG）、498名杂合携带者（CG）和471名非携带者（CC）。BclI基因型在动脉僵硬变量方面未显示出显著差异（例如，颈动脉扩张系数（DC）：12.41±5.37 vs. 12.87±5.55×10-3/kPa[平均值±标准差]；P = 0.38；纯合子与非携带者）。此外，在心脏结构和功能评估方面未发现明显差异。
尽管BclI与较高的BMI以及一些CVD指标相关，但我们的结果不支持BclI携带者状态与更大程度的动脉僵硬或心脏功能障碍相关的概念。
