A favorable cardiometabolic profile is associated with the G allele of the genetic variant rs5068 in African Americans: The Multi-Ethnic Study of Atherosclerosis (MESA).

Valentina Cannone,John C Burnett,Suzette J Bielinski,Christopher G Scott,Thomas J Wang,Deepak K Gupta,Kent D Taylor,Walter Palmas,Nicholas B Larson,Paul A Decker,Víctor Sánchez-Margalet

doi:10.1371/journal.pone.0189858

Abstract

In whites, the minor G allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with higher circulating levels of ANP and B-type natriuretic peptide (BNP), lower risk of hypertension, higher high-density lipoprotein (HDL) cholesterol plasma levels, and lower prevalence of obesity and metabolic syndrome. The observed phenotype is consistent with the blood pressure lowering and metabolic properties of ANP and BNP. The cardiovascular and metabolic phenotype associated with rs5068 genotypes in African Americans is undefined. We genotyped 1631 African Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) for rs5068 and investigated their phenotype. Genotype frequencies of rs5068 were 93.2% AA (n = 1520), 6.7% AG (n = 110) and 0.1% GG (n = 1). All subsequent analyses are AG + GG versus AA genotype. Using a Bonferroni corrected level of significance of 0.005, the prevalence of metabolic syndrome (23% vs 38%, age-sex-adjusted p = 0.002) and triglycerides plasma values (76 vs 90 mg/dl, age-sex-BMI adjusted p = 0.004) were both significantly lower in the AG+GG genotypes. In the AG+GG genotypes, the prevalence of diabetes (8% vs 18%, age-sex-BMI-adjusted p = 0.02) and insulin plasma levels tended to be lower (4.8 vs 5.7 μU/ml, age-sex-BMI adjusted p = 0.04) whereas HDL-cholesterol levels tended to be higher (55 vs 50 mg/dl, age-sex-BMI-adjusted p = 0.04). No association was found with hypertension. The association between the rs5068 G allele and a favorable metabolic phenotype is now shown in African Americans. The rs5068 AG+GG genotypes are associated with lower prevalence of metabolic syndrome and lower triglycerides values.

Highlights

The natriuretic peptides (NP) atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP) are cardiac hormones with well-known blood pressure lowering and natriuretic properties.[1]
Values given are n (%) for categorical variables and mean for continuous variables unless otherwise noted. *P value obtained from univariate regression analysis. † P value obtained from regression analysis adjusted for age and sex. **Variable expressed as median. §Analysis in a subgroup of subjects with known glucose levels and free of diabetes mellitus (n = 1,351). #Analysis in a subgroup of subjects with known insulin levels and free of diabetes mellitus (n = 1,349)
Our study for the first time analyzed the metabolic and cardiovascular phenotype associated with rs5068 genotypes in African Americans, which represent an ethnic group at high risk for cardiovascular and metabolic disease

Summary

Introduction

The natriuretic peptides (NP) atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP) are cardiac hormones with well-known blood pressure lowering and natriuretic properties.[1]. Studies have shown that in the presence of high-fat diet, overexpression of BNP prevents mice from developing obesity and insulin resistance by promoting muscle mitochondrial biogenesis and fat oxidation.[2] Further, Bordicchia and co-workers reported that NP favor browning of white adipocytes inducing thermogenic energy expenditure.[3] Importantly, in human adipocytes, insulin may up-regulate the NP clearance receptor that would increase the clearance of circulating ANP and BNP and reduce their availability and metabolic actions.[4] The single nucleotide polymorphism rs5068 is a genetic variant of the ANP gene (NPPA) which includes the AA, AG and GG genotypes with the G allele being the minor allele. The cardiovascular and metabolic phenotype associated with rs5068 minor allele is consistent with the blood pressure lowering, lipolytic and insulin sensitivity enhancing properties of ANP and BNP via the GC-A.[1, 10, 11]

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Results

Conclusion