HFE gene mutations in a population of Italian Parkinson's disease patients

被引:23
作者
Biasiotto, Giorgio [1 ,2 ]
Goldwurm, Stefano [3 ]
Finazzi, Dario [1 ,2 ]
Tunesi, Sara [3 ,4 ]
Zecchinelli, Anna [3 ]
Sironi, Francesca [3 ,5 ]
Pezzoli, Gianni [3 ]
Arosio, Paolo [1 ,2 ]
机构
[1] Univ Brescia, Dipartimento Mat Infantile & Tecnol Biomed, I-25123 Brescia, Italy
[2] III Lab Anal Chim Clin, Brescia, Italy
[3] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy
[4] Univ Milan, Inst Med Stat & Biometry GA Maccaro, Milan, Italy
[5] Fdn IRCCS Osped Maggiore Policlin, Med Genet Lab, Milan, Italy
关键词
Parkinson's disease; iron; HFE gene; DNA mutations; DHPLC;
D O I
10.1016/j.parkreldis.2007.10.011
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:426 / 430
页数:5
相关论文
共 35 条
[1]   Prevalence of haemochromatosis gene mutations in Parkinson's disease [J].
Aamodt, Anne Hege ;
Stovner, Lars Jacob ;
Thorstensen, Ketil ;
Lydersen, Stian ;
White, Linda R. ;
Aasly, Jan O. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2007, 78 (03) :315-317
[2]   Screening for mutations of the HFE gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra [J].
Akbas, Nilguen ;
Hochstrasser, Helmine ;
Deplazes, Joelle ;
Tomiuk, Juergen ;
Bauer, Peter ;
Walter, Uwe ;
Behnke, Stefanie ;
Riess, Olaf ;
Berg, Daniela .
NEUROSCIENCE LETTERS, 2006, 407 (01) :16-19
[3]   The basal ganglia in haemochromatosis [J].
Berg, D ;
Hoggenmüller, U ;
Hofmann, E ;
Fischer, R ;
Kraus, M ;
Scheurlen, M ;
Becker, G .
NEURORADIOLOGY, 2000, 42 (01) :9-13
[4]  
Berg Daniela, 2006, Top Magn Reson Imaging, V17, P5, DOI 10.1097/01.rmr.0000245461.90406.ad
[5]   Hemochromatosis: Genetics and pathophysiology [J].
Beutler, E .
ANNUAL REVIEW OF MEDICINE, 2006, 57 :331-347
[6]   Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload [J].
Biasiotto, G ;
Belloli, S ;
Ruggeri, G ;
Zanella, I ;
Gerardi, G ;
Corrado, M ;
Gobbi, E ;
Albertini, A ;
Arosio, P .
CLINICAL CHEMISTRY, 2003, 49 (12) :1981-1988
[7]   Association study between iron-related genes polymorphisms and Parkinson's disease [J].
Borie, C ;
Gasparini, F ;
Verpillat, P ;
Bonnet, AM ;
Agid, Y ;
Hetet, G ;
Brice, A ;
Dürr, A ;
Grandchamp, B .
JOURNAL OF NEUROLOGY, 2002, 249 (07) :801-804
[8]  
Bradbury R, 2000, Hum Mutat, V15, P120, DOI 10.1002/(SICI)1098-1004(200001)15:1<120::AID-HUMU32>3.0.CO
[9]  
2-B
[10]   The Cys282Tyr polymorphism in the HFE gene in Australian Parkinson's disease patients [J].
Buchanan, DD ;
Silburn, PA ;
Chalk, JB ;
Le Couteur, DG ;
Mellick, GD .
NEUROSCIENCE LETTERS, 2002, 327 (02) :91-94