title: HFE gene mutations in a population of Italian Parkinson's disease patients.
abstract: An abnormal accumulation and distribution of brain iron are common to different neurodegenerative disorders, including Parkinson's disease (PD), and alteration of genes involved in iron metabolism cause neurodegeneration with brain iron accumulation. HFE participates in the regulation of iron metabolism, its mutations are primary cause of hereditary hemochromatosis and appear to be more frequent in neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis. However, conflicting results were obtained in previous studies aimed to verify if nucleotide variations in HFE gene act as risk modifiers for PD. We used denaturing HPLC for scanning DNA sequence variations in exon 2 and 4 of HFE gene in a cohort of 475 Italian PD patients. We identified the most common H63D, C282Y and S65C, and also other 4 rare mutation types (R66H, R224W, E277K, and T281M). The allele frequency of H63D and C282Y was not statistically different from that of 2 control groups with similar mean age or of a large cohort of the same geographical area. In addition we could not find statistical differences in the clinical phenotypes of patients carrying at least one mutated HFE allele from those with the normal allele. We conclude that in the Italian population, the most common HFE mutations, H63D and C282Y are not associated with the individual risk to develop PD, nor have specific influence on the clinical features of the disease.
authors.affiliation: Dipartimento Materno Infantile e Tecnologie Biomediche, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.forename: Dario
authors.initials: D
authors.lastname: Finazzi
authors.forename: Sara
authors.initials: S
authors.lastname: Tunesi
authors.forename: Anna
authors.initials: A
authors.lastname: Zecchinelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Sironi
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D000071020:Hemochromatosis Protein; D006639:Histidine / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D012694:Serine / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001224:Aspartic Acid; D012694:Serine; D006639:Histidine; D003545:Cysteine