ABSTRACT
PURPOSE: The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans. MATERIALS AND METHODS: To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects. RESULTS: Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4+/-0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant. CONCLUSION: We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.
Subject(s)
Female , Humans , Middle Aged , Alleles , Asian People/genetics , Blood Pressure/genetics , Case-Control Studies , Diastole/genetics , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Hypertension/genetics , Luciferases/metabolism , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Renin/genetics , Republic of Korea , Risk Factors , Systole/genetics , TransfectionABSTRACT
The present study was aimed at investigating the regulation of atrial natriuretic peptide (ANP) system in association with either enhanced or attenuated activity of the renin-angiotensin system (RAS). The cardiac tissue mRNA and peptide levels of ANP were measured in rats with two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension. Plasma renin concentration was increased in 2K1C hypertension along with increases of renin mRNA and protein contents in the clipped kidney. On the contrary, it was suppressed in DOCA-salt hypertension along with decreases of renin mRNA and protein contents in the remaining kidney. The plasma ANP concentration was similarly increased in both models of hypertension. The cardiac tissue ANP contents were not significantly changed, but the tissue ANP mRNA levels were upregulated in the hypertrophied heart in these two models of hypertension. It is suggested that the cardiac ANP system is transcriptionally enhanced by cardiac hypertrophy associated with hypertension, independent of the systemic RAS.
Subject(s)
Male , Rats , Animals , Atrial Natriuretic Factor/metabolism , Desoxycorticosterone , Gene Expression Regulation , Hypertension/metabolism , Hypertension/chemically induced , Myocardium/pathology , Organ Size , Peptides , RNA, Messenger/analysis , Rats, Sprague-Dawley , Renin/genetics , Renin/blood , Renin-Angiotensin System/physiologyABSTRACT
Con el proposito de comprobar agregación familiar de la hipertensión arterial esencial, determinar la presencia de factores genéticos y ambientales en su génesis, y procurar encuadrarlos en un mecanismo de herencia, se estudiaron 108 personas de ambos sexos, entre 21-55 años, 36 de los cuales son hipersensos esenciales, tomados como propósitos, 36 controles de igual edad y sexo y 36 familiares de primer grado de los pacientes. Mediante un estudio caso-control se verificó la presencia o no de factores de riesgo. Se realizó un análisis de regresión logística multivariada para determinar la importancia relativa de los antecedentes familiares de hipertensión dentro de los factores de riesgo. Se llevaron a cabo análisis de caminos y correlaciones canónicas para estudiar asociación entre los antecedentes familiares de hipertensión, cardiopatía isquémica y diabetes mellitus con la tensión arterial sistólica y diastólica. Los principales resultados que obtuvimos fueron que el patrón de herencia es mixto con un componente poligénico y un gen mayor autosómico recesivo, siendo la heredabilidad del 73.80 por ciento. El antecedente familiar de hipertensión constituyó el factor de riesgo más importante de padecer la enfermedad. El índice de masa corporal y el coeficiente cintura-cadera se asocian significativamente con valores de tensión arterial sistólica y diastólica, no ocurriendo así con los lípidos séricos