title: Relationship between ADIPOQ gene, circulating high molecular weight adiponectin and albuminuria in individuals with normal kidney function: evidence from a family-based study.
abstract: OBJECTIVE
  Insulin resistance is associated with reduced serum adiponectin and increased albuminuria levels. Thus, one would anticipate an inverse relationship between circulating adiponectin and albuminuria. However, several studies have described a 'paradoxical' elevation of serum adiponectin in patients with elevated albuminuria. These findings may have been confounded by the presence of diseases and related treatments known to affect circulating adiponectin and albuminuria. We therefore studied the relationship between circulating adiponectin and albuminuria in the absence of such confounders.
  
  
  METHODS
  To this purpose, the relationship between adiponectin isoforms and albumin:creatinine ratio (ACR) was investigated in a family-based sample of 634 non-diabetic untreated white individuals with normal kidney function. We also investigated whether the two variables share a common genetic background and addressed the specific role of the gene encoding adiponectin on that background by genotyping several ADIPOQ single nucleotide polymorphisms (SNPs).
  
  
  RESULTS
  ACR was directly associated with high molecular weight (HMW) adiponectin isoform (p = 0.024). The two variables shared some genetic correlation (ρ(g) = 0.38, p = 0.04). ADIPOQ promoter SNP rs17300539 was associated with HMW adiponectin (p = 4.8 × 10(-5)) and ACR (p =0.0027). The genetic correlation between HMW adiponectin and ACR was no longer significant when SNP rs17300539 was added to the model, thus reinforcing the role of this SNP in determining both traits.
  
  
  CONCLUSIONS
  Our study shows a positive, independent correlation between HWM adiponectin and ACR. ADIPOQ variability is associated with HMW adiponectin and ACR, and explains some of the common genetic background shared by these traits, thus suggesting that ADIPOQ and HMW adiponectin modulate albuminuria levels.
authors.affiliation: Research Unit of Diabetes and Endocrine Disease, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Menzaghi
authors.forename: S
authors.initials: S
authors.lastname: De Cosmo
authors.forename: M
authors.initials: M
authors.lastname: Copetti
authors.forename: L
authors.initials: L
authors.lastname: Salvemini
authors.forename: C
authors.initials: C
authors.lastname: De Bonis
authors.forename: D
authors.initials: D
authors.lastname: Mangiacotti
authors.forename: G
authors.initials: G
authors.lastname: Fini
authors.forename: F
authors.initials: F
authors.lastname: Pellegrini
authors.forename: V
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000235:genetics*; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D052242:Adiponectin; D055316:Cystatin C; D020033:Protein Isoforms; D003404:Creatinine