Tapia-Castillo Alejandra, Carvajal Cristian A, Campino Carmen, Vecchiola Andrea, Allende Fidel, Solari Sandra, García Lorena, Lavanderos Sergio, Valdivia Carolina, Fuentes Cristobal, Lagos Carlos F, Martínez-Aguayo Alejandro, Baudrand Rene, Aglony Marlene, García Hernán, Fardella Carlos E
Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Am J Hypertens. 2014 Mar;27(3):299-307. doi: 10.1093/ajh/hpt277. Epub 2014 Feb 2.
The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G>A) and rs836478 (intron 3, T>C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort.
Two hundred two normotensive (NT) subjects (aged 4-16 years) were divided into 2 groups: NT subjects with hypertensive parents (NH; n = 103) and NT subjects with NT parents (NN; n = 99). We measured markers of inflammation (high-sensitivity C-reactive protein, interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor α), endothelial damage (Plasminogen activator inhibitor-1 metalloproteinase-9, and metalloproteinase-2), and oxidative stress (malondialdehyde). Data were expressed as median and interquartile range (IQR).
We found differences in polymorphism rs836478 (intron 3, C>T) in both genotypic (χ(2) = 15.2, 2 df; P = 0.0005) and allelic (X(2)=5.5, 1 df; P = 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median = 2.3, IQR - 1.6-3.2; vs. median = 1.6, IQR = 1.6-2.3 AU; P = 0.01) and lower IL-6 expression (median = 8.8, IQR = 7.0-11.8; vs. median = 12.1, IQR = 8.2-14.7 pg/ml; P = 0.02) compared with subjects with TC/CC genotype. No difference in the allelic frequency distribution was seen in the polymorphism rs10951982 (NH vs. NN: χ(2)=0.2, 1 df; P = 0.6). For this SNP, NN subjects with GA/AA genotype showed decreased diastolic BP indexes compared with subjects with native GG genotype (median = 1.08, IQR = 1.0-1.2; vs. median = 0.99, IQR = 0.94-1.1; P = 0.02).
We report the frequency of polymorphisms rs836478 and rs10951982 of the RAC1 gene in a Spanish-Amerindian cohort. The polymorphism rs836478 was associated with an increased expression in markers of inflammation and endothelial damage (MMP9 and IL-6) in pediatric subjects with a hypertensive genetic background.
GTP酶Rac1作为盐皮质激素受体活性的调节剂，与高血压有关。我们的目的是研究智利儿科队列中RAC1基因多态性rs10951982（内含子1，G>A）和rs836478（内含子3，T>C）的频率，并进行与临床和生化参数的关联研究。
202名血压正常（NT）的受试者（年龄4至16岁）分为两组：父母患有高血压的NT受试者（NH；n = 103）和父母血压正常的NT受试者（NN；n = 99）。我们测量了炎症标志物（高敏C反应蛋白、白细胞介素6（IL-6）、白细胞介素8和肿瘤坏死因子α）、内皮损伤标志物（纤溶酶原激活物抑制剂-1、金属蛋白酶-9和金属蛋白酶-2）以及氧化应激标志物（丙二醛）。数据以中位数和四分位数间距（IQR）表示。
我们发现rs836478（内含子3，C>T）多态性在NH组与NN组受试者的基因型频率（χ(2)=15.2，2自由度；P = 0.0005）和等位基因频率（X(2)=5.5，1自由度；P = 0.01）上均存在差异。与TC/CC基因型受试者相比，TT基因型的NH受试者MMP9表达增加（中位数 = 2.3，IQR = 1.6 - 3.2；vs.中位数 = 1.6，IQR = 1.6 - 2.3 AU；P = 0.01），IL-6表达降低（中位数 = 8.8，IQR = 7.0 - 11.8；vs.中位数 = 12.1，IQR = 8.2 - 14.7 pg/ml；P = 0.02）。rs10951982多态性的等位基因频率分布在两组间未见差异（NH组与NN组：χ(2)=0.2，1自由度；P = 0.6）。对于该单核苷酸多态性（SNP），与纯合GG基因型受试者相比，GA/AA基因型的NN受试者舒张压指数降低（中位数 = 1.08，IQR = 1.0 - 1.2；vs.中位数 = 0.99，IQR = 0.94 - 1.1；P = 0.02）。
我们报告了西班牙裔-美洲印第安人队列中RAC1基因多态性rs836478和rs10951982的频率。rs836478多态性与具有高血压遗传背景的儿科受试者炎症和内皮损伤标志物（MMP9和IL-6）表达增加相关。
