Givens Raymond C, Lin Yvonne S, Dowling Amy L S, Thummel Kenneth E, Lamba Jatinder K, Schuetz Erin G, Stewart Paul W, Watkins Paul B
General Clinical Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
J Appl Physiol (1985). 2003 Sep;95(3):1297-300. doi: 10.1152/japplphysiol.00322.2003. Epub 2003 May 16.
A single-nucleotide polymorphism (A6986G) in the cytochrome p-450 3A5 (CYP3A5) gene distinguishes an expressor (*1) and a reduced-expressor (*3) allele and largely predicts CYP3A5 content in liver and intestine. CYP3A5 is the prevailing CYP3A isoform in kidney. We report that, among renal microsomes from 21 organ donors, those from *1/*3 individuals had at least eightfold higher mean kidney microsomal CYP3A5 content and 18-fold higher mean CYP3A catalytic activity than did those from *3/*3 individuals (P = 0.0001 and P = 0.0137, respectively). We also report significant associations between the A6986G polymorphism and systolic blood pressure (P = 0.0007), mean arterial pressure (P = 0.0075), and creatinine clearance (P = 0.0035) among 25 healthy African-American adults. These associations remained significant when sex, age, and body mass index were taken into account. The mean systolic blood pressure of homozygous CYP3A5 expressors (*1/*1) exceeded that of homozygous nonexpressors (*3/*3) by 19.3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population.
细胞色素P-450 3A5（CYP3A5）基因中的单核苷酸多态性（A6986G）可区分表达型（*1）和低表达型（*3）等位基因，并在很大程度上预测肝脏和肠道中的CYP3A5含量。CYP3A5是肾脏中主要的CYP3A亚型。我们报告称，在21名器官捐献者的肾微粒体中，*1/3个体的肾微粒体CYP3A5平均含量比3/*3个体至少高8倍，CYP3A催化活性平均高18倍（P分别为0.0001和0.0137）。我们还报告了25名健康非裔美国成年人中A6986G多态性与收缩压（P = 0.0007）、平均动脉压（P = 0.0075）和肌酐清除率（P = 0.0035）之间存在显著关联。在考虑性别、年龄和体重指数后，这些关联仍然显著。纯合CYP3A5表达型（*1/*1）个体的平均收缩压比纯合非表达型（*3/*3）个体高19.3 mmHg。我们推测非裔美国人中高CYP3A5表达型等位基因频率是否可能导致该人群中钠敏感性高血压的高患病率。
