ASSOCIATION OF CYP3A5 GENOTYPES WITH BLOOD PRESSURE AND RENAL FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肾脏细胞色素P450 3A5(CYP3A5)活性与人类的血压和盐敏感性有关。我们在非洲家庭中调查了CYP3A5基因多态性与动态血压(ABP)和肾小球滤过率(GFR)的关系。采用横断面设计，通过塞舌尔(印度洋)的高血压登记招募了72个家庭的375人，每个家庭至少有两个高血压兄弟姐妹。我们从家系数据中分析了CYP3A5等位基因与ABP、GFR和肾脏钠处理(部分锂的排泄)之间的关联，并考虑了其他协变量和家族相关性。CYP3A5携带者日间收缩压和舒张压随年龄增长(0.55和0.23毫米汞柱/年)高于非携带者(0.21和0.04毫米汞/年)。细胞色素P3A5对日间收缩/舒张压有显著的主效应[回归系数分别为-29.6(10.0)/-8.24.1毫米汞柱，P=0.003/0.045]，且这种影响被年龄所修正(细胞色素P3A5x年龄交互作用，P=0.017/0.018)。对于夜间ABP，尿钠排泄量改变了CYP3A5的作用，而年龄不影响其作用。在肾功能方面，携带者的肾小球滤过率比非携带者低7.6ml/min(P=0.045)，近端钠重吸收随年龄增长而降低，而携带者的近端钠重吸收随年龄增加而降低(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，与年龄和钠相关的ABP升高高于非携带者。这种年龄效应可能部分归因于CYP3A5对肾脏钠处理的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We investigated the association of CYP3A5 polymorphisms 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 and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. CYP3A5 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). CYP3A5 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 (CYP3A5 x age interactions, P =0.017/0.018). For night-time ABP, the effect of CYP3A5 was modified by urinary sodium excretion, but not by age. For renal function, CYP3A5 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 in CYP3A5 carriers (P for interaction = 0.02). These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5 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.