NDT Advance Access originally published online on June 8, 2004
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Nephrol Dial Transplant (2004) 19: 2019-2024
Nephrol Dial Transplant Vol. 19 No. 8 © ERA-EDTA 2004; all rights reserved
Original Article
Role of 
-adducin DNA polymorphisms in the genetic predisposition to diabetic nephropathy
1 Nephrology Research Group, Queen's University of Belfast, Northern Ireland and 2 Conway Institute of Biomolecular and Biomedical Research, University College Dublin and the Dublin Molecular Medicine Centre, Irish Republic
Correspondence and offprint requests to: Dr Bryan Conway, Regional Nephrology Unit, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland. Email: BryanConway{at}ntlworld.com
Background. There is substantial evidence for genetic susceptibility to diabetic nephropathy. In particular, genes that predispose to hypertension in the general population may confer susceptibility to nephropathy in patients with diabetes. A Gly460Trp variant in the 
-adducin gene has been associated with essential hypertension. Our aim was to screen the -adducin gene for polymorphisms and to determine if any variants predisposed patients with diabetes to nephropathy. A secondary objective was to assess for association between the Gly460Trp variant and hypertension.
Methods. The exons of the -adducin gene were resequenced in 30 individuals. Selected variants were then genotyped in 155 patients with type 1 diabetes and nephropathy (cases) and 216 persons with type 1 diabetes but no evidence of nephropathy (controls) from Northern Ireland and in 95 cases and 118 controls from the Irish Republic.
Results. Eleven polymorphisms were detected, of which six were novel and three caused amino-acid substitutions. The Gly460Trp and a novel Ser617Cys polymorphism were in strong linkage disequilibrium (D' = 0.98). Neither the genotype nor allele frequencies for the Gly460Trp polymorphism (P = 0.89 and 0.93 respectively) or the Ser617Cys polymorphism (P = 0.46 and 0.76) were significantly different between cases and controls when the Northern Ireland and Irish Republic sample groups were combined. Carriage of the 460Trp allele was not significantly associated with systolic or diastolic blood pressure in either the cases (P = 0.48 and 0.06, respectively) or in the controls (P = 0.50 and 0.94, respectively).
Conclusions. Variation in the -adducin gene does not play a major role in the development of nephropathy in persons with type 1 diabetes in the Irish population. Furthermore, the Gly460Trp variant was not associated with hypertension in this population.
Keywords: -adducin; diabetic nephropathy; genetic susceptibility; hypertension; polymorphism
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  B. R. Conway, D. A. Savage, and A. Peter Maxwell Identifying genes for diabetic nephropathy--current difficulties and future directions Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3012 - 3017. [Full Text] [PDF]
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