Mutation analysis of the HFE gene associated with hereditary hemochromatosis in a Venezuelan sample.
The frequency of the C282Y, H63D and S65C alleles of the HFE gene was determined in a sample of the Venezuelan population. Two new sets of primers were tested for amplifying the regions mapping these mutations, and genotyping was performed by restriction fragment length polymorphism (RFLP). DNA sequencing was used to validate the RFLP analysis. Serum ferritin levels were also determined. Two hundred and fourteen individuals were tested, extracting DNA from whole blood cells (n=177) or from serum (n=37). The frequency of heterozygous subjects was 3.7, 18.2 and 1.7% for the C282Y, H63D and S65C mutations, respectively, and the allele frequencies were 0.019+/-0.01 for C282Y, 0.119+/-0.016 for H63D and 0.009+/-0.005 for S65C. The results suggest that the admixture of native populations with subjects of South European origin might have had an important role in the diffusion of HFE alleles in Venezuela. C282Y homozygous subjects were not found in this study. No HFE genotype studied here was associated with a significant elevation of serum ferritin concentrations, except for C282Y/H63D compound heterozygote found in one asymptomatic male. This finding supports the theory that the H63D mutation could be involved in alterations of iron parameters when inherited together with C282Y. Our results indicate that C282Y homozygotes will be rarely detected. Performance of HFE mutation analysis in individuals with high iron determinations would be recommended.
Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo. 21827, Caracas, 1020-A, Venezuela. evizzi@ivic.ve
Esmeralda
E
Vizzi
Carmen Luisa
CL
Loureiro
Marlene
M
Gerder
María
M
de las Nieves Garcia-Casal
Alvaro
A
Rodríguez-Larralde
Letizia
L
Gerace
Juan Ernesto
JE
Ludert
Ferdinando
F
Liprandi
Flor Helene
FH
Pujol
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011897:Random Allocation; D014687:Venezuela
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron