The Gly460Trp polymorphism and the overnight sodium potassium excretion in hypertensives

Abstract

Abstract Introduction The Gly460Trp polymorphism is associated to hypertension and renal sodium (Na) potassium (K) exchange. This study explores the relationship between blood pressure (BP) and urinary overnight Na/K ratio (UONaK) in patients genotyped for Gly460Trp polymorphism, from a cohort of hypertensive (HT) and normotensive (NT) subjects from National Heart, Lung and Blood Institute funded, Family Blood Pressure Program (FBPP). Hypothesis Abnormal renal K and Na excretion is associated to the Trp allele of Gly460Trp polymorphism. Methods 3,545 subjects genotyped for Gly460Trp polymorphism were analyzed from FBPP. Subjects with diastolic BP (DBP) ≥80 or systolic BP (SBP) ≥130 mmHg were classified HTN; subjects with SBP <130 and DBP <80 mmHg were classified as NT. UONAK was calculated by dividing overnight Na by K concentration. Correlation analysis done with partial variables (body mass index, waist hip ratio, overnight urine creatinine). Results In HTN group (n=1,464), 75% had Gly/Gly, 22% Gly/Trp and 3% Trp/Trp. HTN with Gly/Gly showed strong associations between UONaK and DBP (r=0.191 p<0.0001) and SBP (r=0.06, p=0.04); HTN with Gly/Trp showed strong association for DBP (r=0.123 p=0.025) but not for SBP (r=0.07, p=0.188); while HTN with Trp/Trp there was strong inverse association with SBP (r=−0.399, p=0.010; Fig. 1) and none with DBP (r=0.215 p=0.18). In NT group (n=2,081), 69% had Gly/Gly, 28% Gly/Trp and 3% Trp/Trp; NT with Gly/Gly showed strong associations between UONaK and DBP (r=0.104 p<0.0001) and SBP (r=0.09, p=0.0002); NT with Gly/Trp showed strong association for DBP (r=0.146, p=0.0004) but not for SBP (r=0.05, p=0.18); while NT with Trp/Trp showed no association with DBP (r=−0.003 p=97), or SBP (r=0.06, p=0.61). Conclusions Hypertensives with Trp/Trp showed strong correlation between systolic blood pressure and UONaK, indicating abnormal K excretion in hypertensives, and possible subgroup targeted to potassium sparing drugs. Funding Acknowledgement Type of funding source: None