The A142V Polymorphism of the G Protein Coupled Receptor Kinase 4 Gene Predicts Natriuretic Response to Saline Challenge in Young Normotensive Lean Black and White South African Men

Rayner, B.; Musekiwa, A.; Lombard, C.; Ramesar, R.S.

Nephrology Research and Reviews 3(1): 49-53

2011


DOI: 10.4081/nr.2011.e9
Accession: 068492332

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Abstract
Sensitivity to salt is common in Blacks. We aimed to determine if blood pressure (BP) and natriuretic responses were different in indigeneous Africans (Blacks) compared to Caucasians (Whites), and if this was related to G-protein coupled receptor kinase 4 (GRK-4)polymorphisms. Sixty healthy White and Black men received 2 liters normal saline over 2 h. Baseline demographics, sodium (Na), potassium (K), renin, and aldosterone were recorded. BP, urine output, and urinary Na were measured hourly for 4 h, and renin and aldosterone repeated at 4 h. The R65L and A142V polymorphisms of the GRK-4 gene were determined. At baseline, Blacks had significantly higher diastolic Bp (77 vs 71.2 mm Hg, P<0.002) and K (4.57 vs 4.32 mmol/L, P=0.01), and lower aldosterone levels (132.6 vs 298.3 pmol/L, P<0.0001). After saline challenge, the incremental increase of Na excretion was blunted in Blacks, and there was greater suppression of aldosterone levels. The R65L polymorphism had no effect on natriuresis or aldosterone. Incremental Na excretion was highest in the CC, intermediate in the Ct and lowest in the Tt of the A142V polymorphisms (P<0.001). Aldosterone levels were highest in the Cc group, intermediate in the CT, and lowest in the Tt (P<0.001). The CT/Tt genotypes were significantly more common in Blacks (P<0.001). Black subjects have different natriuretic and aldosterone responses to saline challenge. This appears to be determined by A142V polymorphisms.