Genomic and metabolomic profile associated to microalbuminuria

PLoS One. 2014 Jun 11;9(2):e98227. doi: 10.1371/journal.pone.0098227. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Albuminuria / blood
  • Albuminuria / diagnosis
  • Albuminuria / genetics*
  • Albuminuria / metabolism*
  • Female
  • Genomics
  • Genotype
  • Humans
  • Male
  • Metabolome*
  • Metabolomics
  • Middle Aged
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Nerve Tissue Proteins / genetics
  • Peptidyl-Dipeptidase A / genetics
  • Polymorphism, Single Nucleotide*
  • Rabphilin-3A
  • Vesicular Transport Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Nerve Tissue Proteins
  • Vesicular Transport Proteins
  • ACE protein, human
  • Peptidyl-Dipeptidase A

Grants and funding

The study has been funded by the Ingenious Hypercare Network of Excellence, Life sciences, genomics and biotechnology for health, 6th Framework Programme; EU-MASCARA HEALTH, 2011.2.4.2-2 European Commission, 7th Framework Programme; and the grants PS09/02014, SAF2011-23029 and PI 12/02615. The funders had no role in the study design, data collection andanalysis, decision to publish, or preparation of the manuscript.