RESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Pressão Sanguínea/genética , Diabetes Mellitus Tipo 1/genética , Neuropatias Diabéticas/genética , Receptores de Dopamina D2/genética , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 1/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Finlândia , Humanos , Masculino , Polimorfismo Genético , Receptores de Dopamina D3RESUMO
OBJECTIVE: Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population. RESULTS: The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA(1c) 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA(1c) (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses. CONCLUSIONS: We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
