Bochud Murielle, Eap Chin B, Elston Robert C, Bovet Pascal, Maillard Marc, Schild Laurent, Shamlaye Conrad, Burnier Michel
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
J Hypertens. 2006 May;24(5):923-9. doi: 10.1097/01.hjh.0000222763.84605.4a.
Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families.
Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations.
CYP3A51 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A51 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A51 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A51 was modified by urinary sodium excretion, not by age. For renal function, CYP3A51 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A51 carriers (P for interaction = 0.02).
These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.
肾细胞色素P450 3A5（CYP3A5）活性与人类血压及盐敏感性相关。我们研究了在非洲家庭中，CYP3A5基因多态性是否与动态血压（ABP）及肾小球滤过率（GFR）相关。
采用横断面设计，通过塞舌尔（印度洋）的高血压登记系统招募了来自72个家庭的375名个体，每个家庭至少有两名高血压患者同胞。我们根据家系数据，分析了CYP3A5等位基因（*1、*3、6和7）与ABP、GFR及肾脏钠处理（锂的分数排泄）之间的关联，并考虑了其他协变量和家族相关性。
与非携带者（分别为0.21和0.04 mmHg/年）相比，CYP3A51携带者的日间收缩压和舒张压随年龄增长升高幅度更大（分别为0.55和0.23 mmHg/年）。CYP3A51对日间收缩压/舒张压有显著的主要影响[回归系数（标准误）：-29.6（10.0）/-8.2（4.1）mmHg，P分别为0.003/0.045]，且该效应受年龄影响（CYP3A51×年龄交互作用，P = 0.017/0.018）。对于夜间ABP，CYP3A51的效应受尿钠排泄影响，而非年龄。对于肾功能，CYP3A51携带者的GFR比非携带者低7.6（3.8）ml/min（P = 0.045）。在非携带者中，近端钠重吸收随年龄下降，但在CYP3A51携带者中并非如此（交互作用P = 0.02）。
这些数据表明，CYP3A5基因多态性与动态血压相关，CYP3A5*1携带者的ABP较非携带者表现出更高的与年龄和钠相关的升高幅度。年龄效应可能部分归因于CYP3A5对肾脏钠处理的作用。
