Methylenetetrahydrofolate reductase 677 T allele protects against persistent HBV infection in West Africa.
OBJECTIVE
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.
Bronowicki
Jean-Pierre
JP
Inserm U724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henri Poincaré of Nancy, Vandoeuvre lès Nancy, France. jp.bronowicki@chu-nancy.fr
Abdelmouttaleb
Idrissia
I
Peyrin-Biroulet
Laurent
L
Venard
Véronique
V
Khiri
Hacène
H
Chabi
Nicodème
N
Amouzou
Emile K
EK
Barraud
Hélène
H
Halfon
Philippe
P
Sanni
Ambaliou
A
Bigard
Marc-André
MA
Le Faou
Alain
A
Guéant
Jean-Louis
JL
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000483:Alleles; D001541:Benin / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000235:genetics*; D015342:DNA Probes; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005492:Folic Acid / Q000097:blood; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006509:Hepatitis B / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007118:Immunoassay; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009017:Morbidity; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014805:Vitamin B 12 / Q000097:blood
D015415:Biomarkers; D015342:DNA Probes; D004279:DNA, Viral; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens; D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12