1. Polymorphisms in the rac1 gene are associated with hypertension risk factors in a chilean pediatric population
- Author
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Rene Baudrand, Lorena García, Hernán García, Carlos E. Fardella, Andrea Vecchiola, Alejandra Tapia-Castillo, Carlos F. Lagos, Carmen Campino, Alejandro Martinez-Aguayo, Marlene Aglony, Cristian A. Carvajal, Fidel Allende, Cristobal A. Fuentes, Carolina Valdivia, Sandra Solari, and Sergio Lavanderos
- Subjects
Oncology ,Male ,rac1 GTP-Binding Protein ,medicine.medical_specialty ,Pathology ,Adolescent ,Blood Pressure ,Polymorphism, Single Nucleotide ,Risk Assessment ,chemistry.chemical_compound ,Gene Frequency ,Polymorphism (computer science) ,Risk Factors ,Internal medicine ,Genotype ,Internal Medicine ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,Chile ,Interleukin 6 ,Child ,Gene ,Chi-Square Distribution ,biology ,business.industry ,C-reactive protein ,Introns ,Pedigree ,Blood pressure ,Cross-Sectional Studies ,Phenotype ,chemistry ,Plasminogen activator inhibitor-1 ,Child, Preschool ,Cohort ,Hypertension ,biology.protein ,Disease Progression ,Female ,Inflammation Mediators ,business ,Biomarkers - Abstract
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, GA) and rs836478 (intron 3, TC) 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, CT) 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.
- Published
- 2014