Affiliation:
1. 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.
Abstract
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 (
A
1
) 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
A
1
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 (
T
708
) 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
39 articles.
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