C282Y and H63D mutations of HFE gene in patients with advanced alcoholic liver disease.
OBJECTIVE
To test the hypothesis that the heterozygous state for HFE gene mutations involved in the pathogenesis of hemochromatosis, that may induce an increase of hepatic iron content, may aggravate the liver damage induced by prolonged and excessive use of ethanol.


METHODS
C282Y and H63D mutations of HFE gene were identified through polymerase chain reaction (PCR) on leukocyte DNA, in 125 consecutive patients diagnosed of advanced alcoholic liver disease (109 men, mean age 54 years, SD 11) and 181 healthy controls. All subjects were white Spaniards. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) mutation C282Y: no homozygotes, 10/23 heterozygotes, 115/158 normal (p = 0.60); b) mutation H63D: 9/5 homozygotes, 46/52 heterozygotes, 70/124 normal (Chi square 6.51, p = 0.039). 2. Allele frequencies: a) mutation C282Y: 240/339 normal, 10/23 mutated (p = 0.21); b) mutation H63D: 186/300 normal, 64/62 mutated (odds ratio 1.66, 95% CI 1.10-2.52, p = 0.01).


CONCLUSIONS
Our results suggest that H63D mutation of the HFE gene, but not the C282Y mutation, is associated to the risk of developing advanced liver alcoholic disease.
Ropero Gradilla
P
P
Services of Hematology, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain.
Villegas Martínez
A
A
Fernández Arquero
M
M
García-Agúndez
J A
JA
González Fernández
F A
FA
Benítez Rodríguez
J
J
Díaz-Rubio
M
M
de la Concha
E G
EG
Ladero Quesada
J M
JM
D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D004247:DNA