Byrd James Brian, Auchus Richard J, White Perrin C
From the*University of Michigan, Ann Arbor, MI; and †University of Texas Southwestern Medical Center, Dallas, TX.
J Investig Med. 2015 Oct;63(7):862-6. doi: 10.1097/JIM.0000000000000220.
A single-nucleotide polymorphism in the aldosterone synthase gene (CYP11B2) promoter [-344C/T, rs1799998] has been reported to associate with cardiovascular phenotypes.
The Dallas Heart Study is a large, multiethnic cohort with a high prevalence of hypertension. We genotyped 3452 Dallas Heart Study participants for -344C/T. Generalized linear models were used to assess whether variation at -344C/T associated with plasma aldosterone concentration (PAC), systolic and diastolic blood pressure (SBP and DBP), plasma glucose (in persons with no diabetes), HOMA IR (Homeostasis Model Assessment as an Index of Insulin Resistance), and left ventricular (LV) mass indexed to height. Systolic blood pressure and DBP were significantly higher in blacks compared with whites (P < 0.001 for SBP and for DBP) and Hispanics (P < 0.001 for SBP and for DBP). Log-transformed body mass index was also significantly higher in blacks compared with whites (P < 0.001), but not Hispanics (P = 0.10). Log-transformed PAC was higher in whites compared with blacks (P < 0.001), but did not differ significantly in whites compared with Hispanics (P = 0.73). In univariate and multivariable analysis, -344C/T was not significantly associated with PAC within any ethnicity. In univariate and multivariable analysis, -344C/T was not associated with SBP or DBP within any ethnicity. After adjustment for multiple testing, univariate and multivariable analyses revealed no association between -344C/T and plasma glucose in patients with no diabetes, HOMA IR, or LV mass indexed to height.
We were unable to reproduce previously reported associations between -344C/T and PAC, blood pressure, plasma glucose, or LV mass. Methodological differences might explain the differences between our findings and those previously reported.
醛固酮合酶基因(CYP11B2)启动子中的单核苷酸多态性[-344C/T,rs1799998]已被报道与心血管表型相关。
达拉斯心脏研究是一个大型的多民族队列,高血压患病率很高。我们对3452名达拉斯心脏研究参与者进行了-344C/T基因分型。使用广义线性模型评估-344C/T处的变异是否与血浆醛固酮浓度(PAC)、收缩压和舒张压(SBP和DBP)、血浆葡萄糖(无糖尿病者)、HOMA-IR(稳态模型评估作为胰岛素抵抗指数)以及身高校正后的左心室(LV)质量相关。与白人相比,黑人的收缩压和舒张压显著更高(SBP和DBP的P<0.001),与西班牙裔相比也是如此(SBP和DBP的P<0.001)。黑人的对数转换体重指数也显著高于白人(P<0.001),但高于西班牙裔时差异不显著(P = 0.10)。与黑人相比,白人的对数转换PAC更高(P<0.001),但与西班牙裔相比差异不显著(P = 0.73)。在单变量和多变量分析中,-344C/T在任何种族内均与PAC无显著关联。在单变量和多变量分析中,-344C/T在任何种族内均与SBP或DBP无关。在进行多重检验校正后,单变量和多变量分析显示,-344C/T与无糖尿病患者的血浆葡萄糖、HOMA-IR或身高校正后的LV质量之间无关联。
我们无法重现先前报道的-344C/T与PAC、血压、血浆葡萄糖或LV质量之间的关联。方法学差异可能解释了我们的研究结果与先前报道结果之间的差异。