title: 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.
authors.affiliation: Metabolomic and Molecular Image Lab, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Vannina G
authors.initials: VG
authors.lastname: Marrachelli
authors.affiliation: Metabolomic and Molecular Image Lab, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Monleon
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Rentero
authors.affiliation: Department of Nutrition, Food Science and Physiology. University of Navarra, Pamplona, Spain; CIBERObn, Health Institute Carlos III, Madrid, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Mansego
authors.affiliation: Metabolomic and Molecular Image Lab, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Morales
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Inma
authors.initials: I
authors.lastname: Galan
authors.affiliation: Metabolomic and Molecular Image Lab, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Remedios
authors.initials: R
authors.lastname: Segura
authors.affiliation: CIBERObn, Health Institute Carlos III, Madrid, Spain; Hypertension Unit, Internal Medicine, Hospital Clinico, Valencia, University of Valencia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Internal Medicine, Hospital Rio Hortega, Valladolid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martin-Escudero
authors.affiliation: Hypertension Unit, Internal Medicine, Hospital Clinico, Valencia, University of Valencia, Spain.
authors.forename: Laisa
authors.initials: L
authors.lastname: Briongos
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Health Research Institute, INCLIVA, Valencia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Marin
authors.affiliation: CIBERObn, Health Institute Carlos III, Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lliso
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Health Research Institute, INCLIVA, Valencia, Spain; CIBERDem, Health Institute Carlos III, Madrid, Spain.
authors.forename: Felipe Javier
authors.initials: FJ
authors.lastname: Chaves
authors.affiliation: CIBERObn, Health Institute Carlos III, Madrid, Spain; Hypertension Unit, Internal Medicine, Hospital Clinico, Valencia, University of Valencia, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Redon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D033921:Vesicular Transport Proteins / Q000235:genetics; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; D007703:Peptidyl-Dipeptidase A; D033921:Vesicular Transport Proteins; D000097624:Rabphilin-3A; C488034:ACE protein, human