The Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Am J Hypertens. 2012 Sep;25(9):986-93. doi: 10.1038/ajh.2012.69. Epub 2012 Jun 7.
Both endogenous ouabain (EO) and aldosterone are steroid hormones which might play a role in the pathogenesis of left ventricular (LV) hypertrophy and cardiac remodeling. Cholesterol side-chain cleavage enzyme (CYP11A1) and 3β-hydroxysteroid dehydrogenase (HSD3B1) are two key enzymes in the pathway of steroid biosynthesis.
We investigated in 532 individuals (mean age, 50.3 years; 51.5% women) randomly recruited from a white European population whether LV structure and function were related to genetic variations in CYP11A1 and HSD3B1. We measured LV structure by conventional echocardiography and LV diastolic function by Doppler imaging of the transmitral blood flow and the mitral annular movement. We genotyped tag single nucleotide polymorphisms (SNPs) rs2279357, rs11638442 and rs2073475 in CYP11A1, and rs2236780, rs3765945, and rs6203 in HSD3B1.
While adjusting for covariables and accounting for family clusters, LV mass index decreased (P ≤ 0.049) across the CYP11A1 genotypes in rs2279357 (CC vs. CT vs. TT), rs11638442 (GG vs. GC vs. CC), and rs2073475 (GG vs. GA+AA). Carriers of the CYP11A1 TCG haplotype had lower (P ≤ 0.017) LV mass and LV mass index than noncarriers. Carriers of HSD3B1 GCC haplotype had lower peak early (Ea; P = 0.004) and higher peak late (Aa; P = 0.066) diastolic mitral annular velocities and therefore a lower Ea/Aa ratio (P = 0.041) as compared with noncarriers. Neither plasma endogenous ouabain nor 24-h urinary aldosterone were related to any of the SNPs or haplotypes (P ≥ 0.07).
Pending confirmation in other studies, LV mass and LV diastolic function seem to be related to genetic variation in the steroid biosynthesis.
内源性哇巴因（EO）和醛固酮都是甾体激素，可能在左心室（LV）肥厚和心脏重构的发病机制中起作用。胆固醇侧链裂解酶（CYP11A1）和 3β-羟甾脱氢酶（HSD3B1）是甾体生物合成途径中的两个关键酶。
我们在一个随机招募的白种欧洲人群体中调查了 532 人（平均年龄 50.3 岁；51.5%为女性），研究了 CYP11A1 和 HSD3B1 的遗传变异与 LV 结构和功能的关系。我们通过常规超声心动图测量 LV 结构，通过多普勒成像测量二尖瓣血流和二尖瓣环运动来测量 LV 舒张功能。我们对 CYP11A1 的 rs2279357、rs11638442 和 rs2073475 以及 HSD3B1 的 rs2236780、rs3765945 和 rs6203 进行了标签单核苷酸多态性（SNP）基因分型。
在调整协变量并考虑家族聚类后，CYP11A1 的 rs2279357（CC 与 CT 与 TT）、rs11638442（GG 与 GC 与 CC）和 rs2073475（GG 与 GA+AA）基因型中，LV 质量指数呈下降趋势（P≤0.049）。TCG 单倍型携带者的 LV 质量和 LV 质量指数均低于非携带者（P≤0.017）。HSD3B1 GCC 单倍型携带者的二尖瓣前向 E 峰（Ea）和反向 A 峰（Aa）峰值均较低（P=0.004 和 P=0.066），Ea/Aa 比值较低（P=0.041），而非携带者。内源性哇巴因或 24 小时尿醛固酮与任何 SNP 或单倍型均无相关性（P≥0.07）。
在其他研究中得到证实之前，LV 质量和 LV 舒张功能似乎与甾体生物合成的遗传变异有关。
