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(Hypertension. 2001;37:1416.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Polymorphisms in the hANP (Human Atrial Natriuretic Peptide) Gene, Albuminuria, and Hypertension

Monica Nannipieri; Mascia Manganiello; Anna Pezzatini; Alessandra De Bellis; Giuseppe Seghieri; Ele Ferrannini

From the Department of Internal Medicine and Metabolism Unit of the CNR Institute of Clinical Physiology, University of Pisa School of Medicine (M.N., M.M., E.F.); and the Division of Medicine, General Hospital (A.P., A.D.B., G.S.), Pistoia, Italy.

Correspondence to Dr Monica Nannipieri, CNR Institute of Clinical Physiology, Via Savi, 8, 56100 Pisa, Italy. E-mail nannipi{at}ifc.pi.cnr.it

Abstract—Atrial natriuretic peptide (ANP) jointly affects kidney function and blood pressure homeostasis and is a candidate susceptibility gene for both essential hypertension and kidney disease. We evaluated the relation between the ScaI and BstXI polymorphisms of the human ANP (hANP) gene, hypertension, and albuminuria in a clinical cohort of 1033 subjects, including type 1 and type 2 diabetic patients, nondiabetic subjects with essential hypertension, and nondiabetic normotensive control subjects. Microalbuminuria was present in 15%, 29%, and 2%, respectively, of type 1 diabetic, type 2 diabetic, and nondiabetic patients. Macroalbuminuria was present in 9% of type 1 diabetics, 21% of type 2 diabetics, and 31% of nondiabetics. Prevalence of hypertension was 31%, 58%, and 61% in normoalbuminuric, microalbuminuric, and macroalbuminuric subjects, respectively (P<0.0001). Genotype distributions were in Hardy-Weinberg equilibrium in all 4 patient subgroups. The frequency of the ScaI mutated allele (A¹) was significantly lower in hypertensive than in control subjects (11% versus 19%, P=0.018) and in patients with macroalbuminuria (5%) as compared with normoalbuminuric subjects (16%; P<0.0001). In a nominal logistic model adjusting for gender, age, obesity, diabetes, micro/macroalbuminuria, and hypertension, the A¹ allele was independently associated with macroalbuminuria (odds ratio, 0.57; confidence interval, 1.39 to 3.59; P=0.003) but not with hypertension. In the same model, the frequency of the BstXI mutated allele (T⁷⁰⁸) was increased in the presence of microalbuminuria (odds ratio, 2.25; confidence interval, 1.39 to 3.59; P<0.001). We conclude that the mutated genotypes of the ScaI polymorphism are negatively associated with overt nephropathy, whereas the mutated genotypes of BstXI polymorphism are positively associated with microalbuminuria. hANP gene variants may exert a protective effect against the development and progression of kidney damage in diabetes.

Key Words: atrial natriuretic factor • diabetes • albuminuria • hypertension, genetic

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