Abstract 2589: Angiotensinogen Gene Polymorphism in the Promoter Region is Associated with Erythrocyte K Content, Systolic and Diastolic Blood Pressure and Left Ventricular Mass Index
We have previously reported that low erythrocyte potassium content (RBCK) is an intermediate phenotype for hypertension. RBCK is low in hypertensives and their offspring, is bimodally distributed and is related to increased activation of Ca-activated K channels. Polymorphisms of the Angiotensinogen (AGT) gene are also associated with hypertension, and RAAS has an important role in K homeostasis. In this study, we examined the relationship of AGT variants to RBCK.
Methods: Individuals in this study were 292 white participants in the NHLBI Family Blood Pressure Program with BP, ECHO and RBCK measurements. ECHO was performed by trained sonographers and LVMI (g/m2) was calculated according to the formula of Devereux. RBCK was measured by flame photometry and values expressed mmol/l cell. AGT SNPs (RS5046, RS5049, RS5050, RS5051, RS2493134, RS4762, RS2493132 and RS943580) were genotyped using TaqMan. SAS was used for statistical analysis. Association studies between SNPs and phenotypes were carried out using the General Linear Model with Bonferroni correction was used for mean comparison. The statistical significance level was 0.01.
Results: Significant results were obtained with the AGT variant RS5050 located at -20 within the promoter region. The distribution of genotypes was AA = 198, AC = 93 and CC = 1; we grouped AC and CC into a single group (C allele group). Table 1⇓: subjects with the AA genotype had significantly lower RBCK and significant higher SBP, DBP, and LVMI compared to subjects carrying the C allele, independent of age, gender and BMI.
Conclusion: Variation in RBCK is associated with an AGT promoter variant at -20, which is also related to higher blood pressure and LVMI. These results suggest that variation in AGT gene expression may underlie our previous findings of a relationship of low RBCK and hypertension and confirm the utility of RBCK as an intermediate phenotype.