Diabetes, Vol 43, Issue 5 690-695, Copyright © 1994 by American Diabetes Association

ARTICLES

Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I--converting enzyme gene

A Doria, JH Warram and AS Krolewski
Section on Epidemiology and Genetics, Joslin Diabetes Center, Boston, MA 02215.

In search of genetic determinants of susceptibility to diabetic nephropathy, we examined the association between DNA sequence differences at the locus of angiotensin I-converting enzyme (ACE) and renal complications in 151 insulin-dependent diabetes mellitus (IDDM) patients with a diabetes duration of 16-21 years. This nested case-control study included 77 normoalbuminuric control subjects (albumin excretion rate < 30 micrograms/min) and 74 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. DNA from each of these patients was genotyped at the ACE locus by a three-allele restriction fragment-melting polymorphism (RFMP) (Dde I), which we described recently, and a two-allele insertion/deletion recognized as an Xba I restriction fragment-length polymorphism, which has been shown by other investigators to be associated with serum levels of ACE and with risk of myocardial infarction. The least common allele of the Dde I RFMP was significantly more frequent among cases with nephropathy than among normoalbuminuric control subjects (12.8 vs. 4.5%, P < 0.05). The deletion in the ACE gene was also more frequent in case than in control subjects (56.1 vs. 47.4%), but the difference was not statistically significant (P < 0.25) with this sample size. To determine the independence of these associations, the two polymorphisms were analyzed jointly to identify Xba I/Dde I haplotypes. As might be expected, carriers of the Xba I/Dde I '+ =' haplotype had a fourfold risk of developing diabetic nephropathy (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.5-11.0). However, this did not explain all of the excess Xba I '+' allele among cases.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Qian, E. Feldman, S. Pennathur, M. Kretzler, and F. C. Brosius III From Fibrosis to Sclerosis: Mechanisms of Glomerulosclerosis in Diabetic Nephropathy Diabetes, June 1, 2008; 57(6): 1439 - 1445. [Full Text] [PDF]

				K. G. Ewens, R. A. George, K. Sharma, F. N. Ziyadeh, and R. S. Spielman Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test Diabetes, November 1, 2005; 54(11): 3305 - 3318. [Abstract] [Full Text] [PDF]

				N. Takahashi, J. R. Hagaman, H.-S. Kim, and O. Smithies Minireview: Computer Simulations of Blood Pressure Regulation by the Renin-Angiotensin System Endocrinology, June 1, 2003; 144(6): 2184 - 2190. [Abstract] [Full Text] [PDF]

				W. X. Liao and A. C. Roy Lack of association between polymorphisms in the testis-specific angiotensin converting enzyme gene and male infertility in an Asian population Mol. Hum. Reprod., March 1, 2002; 8(3): 299 - 303. [Abstract] [Full Text] [PDF]

				W. Huang, Y. Gallois, N. Bouby, P. Bruneval, D. Heudes, M.-F. Belair, J. H. Krege, P. Meneton, M. Marre, O. Smithies, et al. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse PNAS, October 25, 2001; (2001) 231476798. [Abstract] [Full Text] [PDF]

				D. Frost and W. Beischer Limited Joint Mobility in Type 1 Diabetic Patients: Associations with microangiopathy and subclinical macroangiopathy are different in men and women Diabetes Care, January 1, 2001; 24(1): 95 - 99. [Abstract] [Full Text]

				M. NANNIPIERI, G. PENNO, L. PUCCI, H. COLHOUN, C. MOTTI, A. BERTACCA, L. RIZZO, L. DE GIORGIO, G. ZERBINI, R. MANGILI, et al. Pronatriodilatin Gene Polymorphisms, Microvascular Permeability, and Diabetic Nephropathy in Type 1 Diabetes Mellitus J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1530 - 1541. [Abstract] [Full Text]

				T. Yoshioka, Y.-x. Xu, H. Yoshida, H. Shiraga, T. Muraki, and K. Ito Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schonlein purpura nephritis Arch. Dis. Child., November 1, 1998; 79(5): 394 - 399. [Abstract] [Full Text]

				A. Otani, H. Takagi, K. Suzuma, and Y. Honda Angiotensin II Potentiates Vascular Endothelial Growth Factor–Induced Angiogenic Activity in Retinal Microcapillary Endothelial Cells Circ. Res., March 23, 1998; 82(5): 619 - 628. [Abstract] [Full Text] [PDF]

				X.-H. Huang, A. Salomaki, R. Malin, T. Koivula, H. Jokela, and T. Lehtimaki Rapid Identification of Angiotensin-Converting Enzyme Genotypes by Capillary Electrophoresis Clin. Chem., November 1, 1997; 43(11): 2195 - 2196. [Full Text]

				J. S. Yudkin, C. Andres, V. Mohamed-Ali, M. Gould, A. Panahloo, A. P. Haines, S. Humphries, and P. Talmud The Angiotensin-Converting Enzyme Gene and the Angiotensin II Type I Receptor Gene as Candidate Genes for Microalbuminuria : A Study in Nondiabetic and Non–Insulin-Dependent Diabetic Subjects Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2188 - 2191. [Abstract] [Full Text]

				K. Kario, N. Kanai, S. Nishiuma, T. Fujii, K. Saito, T. Matsuo, M. Matsuo, and K. Shimada Hypertensive Nephropathy and the Gene for Angiotensin-Converting Enzyme Arterioscler. Thromb. Vasc. Biol., February 1, 1997; 17(2): 252 - 256. [Abstract] [Full Text]

				K. J. McLaughlin, P. N. Harden, S. Ueda, J. M. Boulton-Jones, J. M.C. Connell, and A. G. Jardine The Role of Genetic Polymorphisms of Angiotensin-Converting Enzyme in the Progression of Renal Diseases Hypertension, November 1, 1996; 28(5): 912 - 915. [Abstract] [Full Text]

				D. R.J. Singer, C. G. Missouris, and S. Jeffery Angiotensin-Converting Enzyme Gene Polymorphism: What to Do About All the Confusion? Circulation, August 1, 1996; 94(3): 236 - 239. [Full Text]

				A. Doria, T. Onuma, G. Gearin, M. B. S. Freire, J. H. Warram, and A. S. Krolewski Angiotensinogen Polymorphism M235T, Hypertension, and Nephropathy in Insulin-Dependent Diabetes Hypertension, May 1, 1996; 27(5): 1134 - 1139. [Abstract] [Full Text]

				W. Huang, Y. Gallois, N. Bouby, P. Bruneval, D. Heudes, M.-F. Belair, J. H. Krege, P. Meneton, M. Marre, O. Smithies, et al. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse PNAS, November 6, 2001; 98(23): 13330 - 13334. [Abstract] [Full Text] [PDF]