Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma.
OBJECTIVE
To evaluated the association of the risk factors and polymorphisms inMTHFR C677T,MTHFR A1298C,MTR A2756GandMTRR A66Ggenes.


METHODS
Patients with cirrhosis (n= 116), hepatocellular carcinoma (HCC) (n= 71) and controls (n= 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0 and SNPstats were utilized for statistical analysis.


RESULTS
Showed that age ≥ 46 years (OR = 10.31; 95%CI: 5.66-18.76;P< 0.001) and smoking (OR = 0.47; 95%CI: 0.28-0.78;P= 0.003) were associated with cirrhosis. Age ≥ 46 years (OR = 16.36; 95%CI: 6.68-40.05;P< 0.001) and alcohol habit (OR = 2.01; 95%CI: 1.03-3.89;P= 0.039) were associated with HCC.MTHFR A1298Cin codominant model (OR = 3.37; 95%CI: 1.52-7.50;P= 0.014), recessive model (OR = 3.04; 95%CI: 1.43-6.47;P= 0.0051) and additive model (OR = 1.71; 95%CI: 1.16-2.52;P= 0.0072) was associated with HCC, as well asMTR A2756Gin the additive model (OR = 1.68; 95%CI: 1.01-2.77;P= 0.047), andMTRR A66Gin the codominant model (OR = 3.26; 95%CI: 1.54-6.87;P< 0.001), dominant model (OR = 2.55; 95%CI: 1.24-5.25;P= 0.007) and overdominant model (OR = 3.05; 95%CI: 1.66-5.62;P< 0.001).MTR A2756Gin the additive model (OR = 1.54; 95%CI: 1.02-2.33;P= 0.042) and smokers who presented at least one polymorphic allele forMTRR A66G(OR = 1.71; 95%CI: 0.77-3.82;P= 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms.


CONCLUSIONS
Age ≥ 46 years, alcohol habit andMTR A2756G,MTHFR A1298CandMTRR A66Gpolymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and theMTR A2756Gpolymorphism are associated with cirrhosis.
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Nathália Perpétua
NP
Peres
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Ana Lívia Silva
AL
Galbiatti-Dias
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Márcia Maria Urbanin
MM
Castanhole-Nunes
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Renato Ferreira
RF
da Silva
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Érika Cristina
ÉC
Pavarino
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Eny Maria
EM
Goloni-Bertollo
Nathália Perpétua Peres, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo, Mariangela Torreglosa Ruiz-Cintra, Genetics and Molecular Biology Research Unit, UPGEM, São José do Rio Preto 15090-000, Brazil.
Mariangela Torreglosa
MT
Ruiz-Cintra
Folate metabolism; Hepatocellular carcinoma; Liver cirrhosis; Polymorphism