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NDT Advance Access published online on March 5, 2004

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh174
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received August 26, 2003
Accepted January 23, 2004


Original Article

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

Kim J. Pettersson-Fernholm 1, Carol M. Forsblom 1, Markus Perola 2, Johan A. Fagerudd 1, Per-Henrik Groop 1*, for the FinnDiane Study Group

1 Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki; Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
2 UCLA, Department of Human Genetics, Los Angeles, California, USA; Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland

* To whom correspondence should be addressed. E-mail: per-henrik.groop{at}folkhalsan.fi.



  Abstract

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.

Keywords: blood pressure, diabetic nephropathy, dopamine D3 receptor gene, haplotype, linkage disequilibrium, normoalbuminuria, polymorphism, proteinuria, type 1 diabetes


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