Genomic and Metabolomic Profile Associated to Microalbuminuria

Abstract

To identify factors related with the risk to develop microalbuminuria using combined genomic and metabolomic values from a general population study. One thousand five hundred and two subjects, Caucasian, more than 18 years, representative of the general population, were included. Blood pressure measurement and albumin/creatinine ratio were measured in a urine sample. Using SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54±19, 50.6% men, ACR>30 mg/g in 81 subjects) with high genotyping call rate were analysed. A characteristic metabolomic profile, which included products from mitochondrial and extra mitochondrial metabolism as well as branched amino acids and their derivative signals, were observed in microalbuminuric as compare to normoalbuminuric subjects. The comparison of the metabolomic profile between subjects with different UAE status for each of the genotypes associated to microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the rs4359_CC of ACE gene, with minimal or no statistically significant differences. Subjects with and without microalbuminuria, who shared the same genotype and metabolomic profile, differed in age. Microalbuminurics with the CC genotype of the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism were seven years older and seventeen years younger, respectively as compared to the whole microalbuminuric subjects. With the same metabolomic environment, characteristic of subjects with microalbuminuria, the TT genotype of the rs10492025 polymorphism seems to increase and the CC genotype of the rs4359 polymorphism seems to reduce risk to develop microalbuminuria.

The Future of “Omics” in Hypertension

“…Other rodent studies used systems biology approaches to place proteomic data into larger disease pathways, identifying dysregulated networks and predicting further targets from such analyses 46, 47. In human hypertension, 2 recent studies by Marrachelli et al 48, 49. combined metabolomic and genomic data to study factors associated with microalbuminuria and a range of cardiometabolic risk factors.…”

Diastolic Left Ventricular Function in Relation to Circulating Metabolic Biomarkers in a General Population

“…Metabolomics is the systematic study of small‐molecule metabolite profiles in biological fluids . Studies of HF patients matched with healthy controls showed a different metabolic signature in serum and urine .…”

“…Metabolomics is the systematic study of small-molecule metabolite profiles in biological fluids. 7,8 Studies of HF patients matched with healthy controls showed a different metabolic signature in serum 9 and urine. 9,10 Recently, Cheng et al demonstrated that over and beyond classical risk factors and Btype natriuretic peptide (BNP), circulating plasma metabolites had diagnostic value in assessing HF-related metabolic disturbances and predicting hospitalizations and mortality.…”

1.1 Diastolic Left Ventricular Function in Relation to Circulating Metabolic Biomarkers in a General Population

“…For nuclear magnetic resonance (NMR) spectroscopy, 7,16,17 500 lL of plasma were mixed with 50 lL of D 2 O (as a field lock). A total of 500 lL of the mixture of each sample was then individually transferred into a 5-mm high-resolution NMR tube.…”

“…7,8 Studies of HF patients matched with healthy controls showed a different metabolic signature in serum 9 and urine. 9,10 Recently, Cheng et al…”