Dopamine D3 receptor gene polymorphisms, blood pressure and nephropathy in type 1 diabetic patients.

Abstract

Dopamine modulates blood pressure in the kidney. The aim of this study was to investigate whether two previously known (-707 G/C, Ser9Gly) and one novel (Ala17Ala) polymorphism in the dopamine D3 receptor gene and/or their haplotypes are associated with blood pressure, diabetic nephropathy or renal variables in the study subjects. A cross-sectional, case-control study with a total of 996 type 1 diabetic patients from the multicentre, nationwide FinnDiane Study. Patients were recruited consecutively and classified into four groups according to their renal status. The frequencies of the genotypes harbouring the minor allele were 33, 51 and 19% for the -707 G/C, Ser9Gly and Ala17Ala polymorphisms, respectively. Frequencies of the -707 G/C minor genotypes were 35 (normoalbuminuria), 32 (microalbuminuria), 28 (proteinuria) and 39% (end-stage renal disease) (chi(2) = 6.3, df = 3, P = 0.1), of the Ser9Gly 52, 51, 46 and 57% (chi(2) = 6.3, df = 3, P = 0.1) and of the Ala17Ala polymorphism 18, 19, 19 and 21% (chi(2) = 0.7, df = 3, P = 0.9), respectively. Five haplotypes were identified, but no differences were seen between those with and without diabetic nephropathy. Furthermore, there were no differences in blood pressure levels nor in any renal variables between genotypes or haplotypes. These results do not provide evidence for an involvement of the dopamine D3 receptor gene in blood pressure levels or in the pathogenesis of diabetic nephropathy in type 1 diabetic patients.