Methylenetetrahydrofolate reductase 677 T allele protects against persistent HBV infection in West Africa.
Level 4 - case-series / case-control
Cross-sectional genetic association study
PubMed 18222012 · doi:10.1016/j.jhep.2007.11.017
What was done
Four hundred and fifty-five healthy adults from Togo and Benin were evaluated for hepatitis B virus (HBV) serological markers (anti-HBc, anti-HBs, HBsAg), serum folate, vitamin B12, HLA DR alleles, and polymorphisms in one-carbon metabolism: MTHFR 677 C→T, MTHFR 1298 A→C, and methionine synthase 2756 A→G. Stepwise logistic regression was used to identify independent factors associated with HBV infection outcomes.
What was found
Seventy-eight percent of the cohort was anti-HBc positive; among these, 202 (56.9%) were anti-HBs positive and 58 (16.3%) were HBsAg positive. Stepwise logistic regression showed that the MTHFR 677 T allele was independently associated with the persistence of detectable anti-HBs antibodies (OR: 2.47; 95% CI: 1.29–4.71; p=0.006). Among HBsAg-positive subjects, mean HBV DNA levels were significantly lower in 677 T allele carriers than in those with the 677 CC genotype (1,000 ± 1,406 vs. 2,400,000 ± 214,000 copies/mL; p=0.005). Beninese origin and the HLA-DRB1*09 allele were also independently associated with favorable HBV outcomes.
Why it matters
This study links host one-carbon metabolism genetics, specifically the MTHFR 677 T allele, to enhanced viral clearance and lower viral loads in West African adults exposed to HBV.
Limits
The cross-sectional design precludes establishing causality or evaluating longitudinal viral dynamics. Subgroup analysis of HBsAg-positive carriers was limited by a small sample size (n=58), and results from healthy Togolese and Beninese adults may not generalize to other populations or clinical cohorts.
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