title: Association between the HFE mutations and unsuccessful ageing: a study in Alzheimer's disease patients from Northern Italy.
abstract: Mutations in the class I-like Major Histocompatibility Complex gene HFE are associated with hereditary hemochromatosis (HH), a disorder caused by excessive iron uptake. Three common mutations have been found: C282Y, H63D, and S65C. Moreover, several studies have suggested that HFE mutations may be involved in several age-related chronic diseases such as Alzheimer's disease (AD) and coronary heart disease, but apparently paradoxically also with longevity. In particular, in AD, patients carrying the H63D allele have been suggested to have a mean age at onset of 72 vs. 77 years for those who were homozygous for the wild-type allele. Thus, it seems that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals. In the present study, we analysed the HFE genotype in 123 patients with sporadic AD and 152 age-matched controls from Northern Italy. Samples were typed for C282Y, H63D and S65C alleles using the polymerase chain reaction and sequence specific primers. No significant differences were observed in frequencies of the different alleles between controls and AD both for the whole group and when the data were analysed according to gender. In addition, we failed to observe any difference in the age at onset between patients carrying the mutant HFE-H63D allele and those homozygous for the wild-type allele, either in men or women. Also taking into account the presence or absence of the APOE-epsilon 4 allele, no significant differences were observed between carriers of the mutant HFE-H63D allele and those homozygous for the wild-type allele. Thus, our study does not support the suggestion that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals.
authors.affiliation: Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Corso Tukory 211, 90134, Palermo, Italy. gcandore@unipa.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Federico
authors.initials: F
authors.lastname: Licastro
authors.forename: Martina
authors.initials: M
authors.lastname: Chiappelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.forename: Carmela
authors.initials: C
authors.lastname: Rita Balistreri
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Piazza
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Colonna-Romano
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000276:immunology*; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins