title: Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD).
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD.
  
  
  METHODS
  Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson's, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies.
  
  
  RESULTS
  The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005).
  
  
  CONCLUSIONS
  Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.
authors.affiliation: School of Medicine, University of Pernambuco, Pernambuco, Brazil.
authors.forename: Sylene Coutinho Rampche
authors.initials: SC
authors.lastname: de Carvalho
authors.forename: Maria Tereza Cartaxo
authors.initials: MT
authors.lastname: Muniz
authors.forename: Maria Deozete Vieira
authors.initials: MD
authors.lastname: Siqueira
authors.forename: Erika Rabelo Forte
authors.initials: ER
authors.lastname: Siqueira
authors.forename: Adriana Vieira
authors.initials: AV
authors.lastname: Gomes
authors.forename: Karina Alves
authors.initials: KA
authors.lastname: Silva
authors.forename: Laís Carvalho Luma
authors.initials: LC
authors.lastname: Bezerra
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
authors.forename: Claudia Pinto Marques Souza
authors.initials: CP
authors.lastname: de Oliveira
authors.forename: Leila Maria M Beltrão
authors.initials: LM
authors.lastname: Pereira
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D005234:Fatty Liver / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood
chemical_list: D015415:Biomarkers; D014280:Triglycerides; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
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