Methylenetetrahydrofolate reductase 677 T allele protects against persistent HBV infection in West Africa

J Hepatol. 2008 Apr;48(4):532-9. doi: 10.1016/j.jhep.2007.11.017. Epub 2008 Jan 2.

Abstract

Background/aims: Homocysteine metabolism is linked to DNA methylation, a mechanism potentially involved in the course of hepatitis B virus (HBV) infection. We evaluated the association of determinants of homocysteine metabolism with the outcome of HBV infection.

Methods: Four hundred and fifty-five healthy adults from Togo and Benin were tested for HBV serologic markers, HLA DR alleles, folate, vitamin B12, methylenetetrahydrofolate reductase (MTHFR) 677 C-->T, 1298 A-->C and methionine synthase 2756 A-->G polymorphisms.

Results: Seventy-eight percent of the study population was anti-HBc positive. Among them, 202 (56.9%) were anti-HBs positive and 58 (16.3%) were HBsAg positive. After stepwise logistic regression, the MTHFR 677 T allele was independently associated with persistence of detectable anti-HBs antibodies (OR: 2.47; 95% CI: 1.29-4.71; p=0.006). The mean HBV DNA level was significantly lower in HBsAg positive subjects carrying the 677 T allele than in those with the 677 CC genotype (1000+/-1406 vs. 2,400,000+/-214,000 copies/ml, p=0.005). Beninese origin and HLA-DRB1*09 allele were the other determinants independently associated with favorable outcome of HBV infection.

Conclusions: The methylenetetrahydrofolate reductase 677 T allele seems to protect against chronic HBV infection in young African adults.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
  • Adult
  • Alleles
  • Benin / epidemiology
  • Biomarkers / blood
  • DNA / genetics*
  • DNA Probes
  • DNA, Viral / analysis
  • Female
  • Folic Acid / blood
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Hepatitis B / enzymology
  • Hepatitis B / epidemiology
  • Hepatitis B / genetics*
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Homocysteine / blood
  • Humans
  • Immunoassay
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Middle Aged
  • Morbidity
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Vitamin B 12 / blood

Substances

  • Biomarkers
  • DNA Probes
  • DNA, Viral
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Hepatitis B Surface Antigens
  • Homocysteine
  • DNA
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • Vitamin B 12