A polymorphism within the promoter of the dopamine receptor D1 (DRD1 -48A7G) associates with impaired kidney function in white hypertensive patients

Abstract

Dopamine DRD1 receptor regulates renal function and vascular resistance. It plays a role in the pathogenesis of hypertension in animal models. In humans, the DRD1 gene presents a A-48G polymorphism associated to hypertension in a Japanese population. To explore the role of this polymorphism on blood pressure and renal function in Caucasian hypertensive patients (H), we evaluated the allele frequencies in a populations of 697 H and 100 blood volunteers, and found no difference in the distribution of the alleles between the two groups (AA;AG;GG: 13%;50%;37%; and 12%; 51%;36% respectively). In H, we found a significant difference between AA and GG in serum creatinine (AA: 1.06±.08 mg/dl; GG:0.97±0.02 mg/dl, p<0.03). Treatment restored serum creatinine at levels comparable between genotypes (AA: 0.99±0.03 mg/dl; GG: 0.94±0.02 mg/dl, n.s.). To replicate the finding, in a case control study of 8 AA and 7 GG hypertensive patients matched for age, sex and body mass index, in pharmacological wash out for 30 days, we evaluated serum (Creatinine, Na, Uric Acid, Urea) and urinary (volume/24h, protein/24h, creatinine clearance/24h) biochemistry and renal hemodynamic assessed by ultrasound. Once again, the AA group showed higher serum creatinine, Na, Uric acid and urea, reduced creatinine clearance and a higher level of urinary protein excretion. These changes occurred while no differences were observed in diuresis and renal vascular resistances. In conclusions, the DRD1 A-48G polymorphism identifies a class of H that is prone to hypertension related kidney alterations.