title: Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy.
abstract: BACKGROUND
  Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency.
  
  
  METHODS
  Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m(2)), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models.
  
  
  RESULTS
  MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141-1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH.
  
  
  CONCLUSIONS
  Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.
authors.affiliation: Internal Medicine Department, University of Catania, Catania, Italy. trovato.eu@gmail.com
authors.forename: Guglielmo M
authors.initials: GM
authors.lastname: Trovato
authors.forename: Daniela
authors.initials: D
authors.lastname: Catalano
authors.forename: Angela
authors.initials: A
authors.lastname: Ragusa
authors.forename: G Fabio
authors.initials: GF
authors.lastname: Martines
authors.forename: Antonia
authors.initials: A
authors.lastname: Tonzuso
authors.forename: Clara
authors.initials: C
authors.lastname: Pirri
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Buccheri
authors.forename: Concetta
authors.initials: C
authors.lastname: Di Nora
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Trovato
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D004032:Diet; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D051437:Renal Insufficiency / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D002097:C-Reactive Protein; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)