Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population

Tapia-Castillo, A; Carvajal, CA; Campino C.; Vecchiola, A; Allende, F; Solari, S; Garcia, L.; Lavanderos, S; Valdivia C.; Fuentes C.; Lagos, CF; Martinez-Aguayo, A; Baudrand R.; Aglony, M; García H.; et. al.


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 416 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 ), 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 ((2) 15.2, 2df; P 0.0005) and allelic (X(2)5.5, 1df; P 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median 2.3, IQR - 1.63.2; vs. median 1.6, IQR 1.62.3 AU; P 0.01) and lower IL-6 expression (median 8.8, IQR 7.011.8; vs. median 12.1, IQR 8.214.7 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: (2)0.2, 1df; 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 1.01.2; vs. median 0.99, IQR 0.941.1; 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.

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Título según WOS: Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population
Volumen: 27
Número: 3
Fecha de publicación: 2014
Página de inicio: 299
Página final: 307
Idioma: English
URL: http://ajh.oxfordjournals.org/cgi/doi/10.1093/ajh/hpt277


Notas: ISI