Methylenetetrahydrofolate reductase gene polymorphism and serum homocysteine levels in nonalcoholic fatty liver disease.
OBJECTIVE
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by hepatic fat accumulation in the absence of alcohol consumption. Hyperhomocysteinemia is considered an independent risk factor for liver diseases, and the genetic polymorphisms C677T and A1298C in the MTHFR gene have been linked to hyperhomocysteinemia. The purpose of this study was to investigate serum homocysteine (Hcy) concentrations and the MTHFR C677T and A1298C polymorphisms as risk factors for the development of NAFLD.


METHODS
One hundred and thirty-four Brazilian patients with biopsy-proven NAFLD and 134 healthy controls were recruited. The MTHFR C677T and A1298C polymorphisms were detected through polymerase chain reaction restriction fragment length polymorphism. Serum Hcy levels were determined by chemiluminescence.


RESULTS
Serum Hcy levels were higher in NAFLD patients as compared to control subjects, but there were no differences between patients with steatosis and nonalcoholic steatohepatitis. The NAFLD and control groups did not differ in genotypic and allelic frequencies of the MTHFR C677T and A1298C polymorphisms, either. Elevated plasma Hcy levels were positively correlated with age in the NAFLD subjects.


CONCLUSIONS
The MTHFR C677T and A1298C polymorphisms are not genetic risk factors for the development of NAFLD. Higher Hcy levels exist in NAFLD subjects, but they are not associated with liver disease severity.
Nutrology Division, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Maria José
MJ
Franco Brochado
Fernanda Aparecida
FA
Domenici
Ana de Lourdes
Ade L
Candolo Martinelli
Sergio
S
Zucoloto
Selma Freire
SF
de Carvalho da Cunha
Helio
H
Vannucchi
D000328:Adult; D000886:Anthropometry; D001938:Brazil; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)