Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04–7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.
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Original Articles|
September 01 1996
A Molecular Variant of Angiotensinogen Is Associated With Diabetic Nephropathy in IDDM
Damian G Fogarty;
Damian G Fogarty
Regional Nephrology Unit, The Queen's University of Belfast
Belfast, Northern Ireland
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J Camille Harron;
J Camille Harron
Regional Nephrology Unit, The Queen's University of Belfast
Belfast, Northern Ireland
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Anne E Hughes;
Anne E Hughes
Belfast City Hospital, and the Departments of Medical Genetics, The Queen's University of Belfast
Belfast, Northern Ireland
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Norman C Nevin;
Norman C Nevin
Belfast City Hospital, and the Departments of Medical Genetics, The Queen's University of Belfast
Belfast, Northern Ireland
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Ciaran C Doherty;
Ciaran C Doherty
Regional Nephrology Unit, The Queen's University of Belfast
Belfast, Northern Ireland
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A Peter Maxwell
A Peter Maxwell
Medicine, The Queen's University of Belfast
Belfast, Northern Ireland
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Address correspondence and reprint requests to Dr. Damian Fogarty, Regional Nephrology Unit, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland.
Diabetes 1996;45(9):1204–1208
Article history
Received:
August 02 1995
Revision Received:
March 25 1996
Accepted:
March 25 1996
PubMed:
8772723
Citation
Damian G Fogarty, J Camille Harron, Anne E Hughes, Norman C Nevin, Ciaran C Doherty, A Peter Maxwell; A Molecular Variant of Angiotensinogen Is Associated With Diabetic Nephropathy in IDDM. Diabetes 1 September 1996; 45 (9): 1204–1208. https://doi.org/10.2337/diab.45.9.1204
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