Chai Wenxia, Hoedemaekers Yvonne, van Schaik Ron H N, van Fessem Marianne, Garrelds Ingrid M, Saris Jasper J, Dooijes Dennis, ten Cate Folkert J, Kofflard Marcel M J, Danser A H Jan
Department of Pharmacology, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
J Renin Angiotensin Aldosterone Syst. 2006 Dec;7(4):225-30. doi: 10.3317/jraas.2006.042.
Left ventricular (LV) hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors. Here, we determined whether aldosterone modulates hypertrophy in HCM. Cardiac and/or plasma aldosterone were measured in organ donors and HCM patients. The effect of the aldosterone synthase ( CYP11B2 ) C-344T polymorphism on LV mass index (LVMI) and interventricular septum thickness (IVS) was determined in 79 genetically independent subjects with HCM. Aldosterone in HCM hearts and plasma was similar to that in normal hearts and plasma. In HCM women, no associations between CYP11B2 genotype and any of the measured parameters were observed, whereas in HCM men, LVMI increased with the presence of the T allele. Similar T allele-related increases were observed for IVS. Multiple regression analysis revealed that the T allele-related effect on IVS occurred independently of renin, the ACE I/D polymorphism, the AT1-receptor A/C(1166)polymorphism and the AT2-receptor A/C(3123) polymorphism. In conclusion, circulating and cardiac aldosterone are normal in HCM, thereby arguing against selectively increased cardiac aldosterone production in HCM. Thus, the association between the CYP11B2 C-344T polymorphism and hypertrophy in HCM most likely relates to the T allele-related increases in circulating aldosterone. This finding raises the need for studies determining the benefit of aldosterone blockade in HCM.
肥厚型心肌病（HCM）患者的左心室（LV）肥厚情况各不相同，提示存在修饰因子的作用。在此，我们确定醛固酮是否调节HCM中的肥厚。在器官捐献者和HCM患者中测量心脏和/或血浆醛固酮。在79名基因独立的HCM受试者中，确定醛固酮合酶（CYP11B2）C-344T多态性对左心室质量指数（LVMI）和室间隔厚度（IVS）的影响。HCM心脏和血浆中的醛固酮与正常心脏和血浆中的醛固酮相似。在HCM女性中，未观察到CYP11B2基因型与任何测量参数之间的关联，而在HCM男性中，T等位基因的存在会使LVMI增加。IVS也观察到类似的与T等位基因相关的增加。多元回归分析显示，T等位基因对IVS的影响独立于肾素、ACE I/D多态性、AT1受体A/C(1166)多态性和AT2受体A/C(3123)多态性。总之，HCM患者循环和心脏中的醛固酮正常，因此反对HCM中心脏醛固酮产生选择性增加的观点。因此，CYP11B2 C-344T多态性与HCM肥厚之间的关联很可能与循环醛固酮中与T等位基因相关的增加有关。这一发现增加了确定醛固酮阻断在HCM中的益处的研究的必要性。
