title: -374 T/A RAGE polymorphism is associated with chronic kidney disease progression in subjects affected by nephrocardiovascular disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) patients present elevated advanced glycation end products (AGEs) blood levels. AGEs promote inflammation through binding to their receptor (RAGE), located on the membrane of mesangial cells, endothelial cells and macrophages. Several genetic polymorphisms influence RAGE transcription, expression and activity, including the substitution of a thymine with an adenine (T/A) in the position -374 of the gene promoter of RAGE. Our study investigates the role of -374 T/A RAGE polymorphism in CKD progression in subjects affected by nephrocardiovascular disease.
  
  
  METHODS
  174 patients (119 males (68.4%) mean age 67.2±0.88 years; 55 females (31.6%): mean age 65.4±1.50 years) affected by mild to moderate nephrocardiovascular CKD were studied. Each subject was prospectively followed for 84 months, every 6-9 months. The primary endpoint of the study was a rise of serum creatinine concentrations above 50% of basal values or end stage renal disease.
  
  
  RESULTS
  Carriers of the A/A and T/A genotype presented higher plasma levels of interleukin 6 (A/A 29.5±15.83; T/A 30.0±7.89, vs T/T 12.3±5.04 p = 0.01 for both) and Macrophages chemoattractant protein 1 (A/A 347.1±39.87; T/A 411.8±48.41, vs T/T 293.5±36.20, p = 0.04 for both) than T/T subjects. Carriers of the A allele presented a faster CKD progression than wild type patients (Log-Rank test: Chi square = 6.84, p = 0,03). Cox regression showed that -374 T/A RAGE polymorphism (p = 0.037), albuminuria (p = 0.01) and LDL cholesterol (p = 0.038) were directly associated with CKD progression. HDL cholesterol (p = 0.022) and BMI (p = 0.04) were inversely related to it. No relationship was found between circulating RAGE and renal function decline.
  
  
  CONCLUSIONS
  -374 T/A RAGE polymorphism could be associated with CKD progression and inflammation. Further studies should confirm this finding and address whether inhibiting RAGE downstream signalling would be beneficial for CKD progression.
authors.affiliation: Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. ivano.baragetti@icp.mi.it
authors.forename: Ivano
authors.initials: I
authors.lastname: Baragetti
authors.forename: Giuseppe Danilo
authors.initials: GD
authors.lastname: Norata
authors.forename: Cristina
authors.initials: C
authors.lastname: Sarcina
authors.forename: Andrea
authors.initials: A
authors.lastname: Baragetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Rastelli
authors.forename: Laura
authors.initials: L
authors.lastname: Buzzi
authors.forename: Liliana
authors.initials: L
authors.lastname: Grigore
authors.forename: Katia
authors.initials: K
authors.lastname: Garlaschelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Pozzi
authors.forename: Alberico Luigi
authors.initials: AL
authors.lastname: Catapano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002318:Cardiovascular Diseases / Q000150:complications* / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics* / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality
chemical_list: D000067759:Receptor for Advanced Glycation End Products