Association study between iron-related genes polymorphisms and Parkinson's disease

Borie, Claire; Gasparini, Francesca; Verpillat, Patrice; Bonnet, Anne‐Marie; Agid, Yves; Hetet, Gilles; Brice, Alexis; Dürr, Alexandra; Grandchamp, Bernard

doi:10.1007/s00415-002-0704-6

Cited by 104 publications

(66 citation statements)

References 15 publications

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“…This result contrasts with previous findings where increased GG genotype was found in the PD group over 60 years at onset[2]. On the basis of the reported odds ratio in the results of Borie et al[2] our study had a power of 0.42 to detect statistically LETTER TO THE EDITORS JON 1695 genotypic differences. Our results suggest that the G258S transferrin polymorphism does not behave as a genetic risk factor for either sporadic or familial PD.…”

contrasting

confidence: 82%

“…In a recent genetic association study, the G258S transferrin polymorphism has been associated to PD particularly among cases with onset after age 60 years and with negative family history [2]. Transferrin is involved in iron uptake via the transferrin receptor, intracellular iron processing and possibly in iron efflux [1,6].…”

mentioning

confidence: 99%

“…DNA was obtained from leukocytes by standard procedures. Genotyping of the transferrin polymorphism was performed as previously described [2]. Statistical assessment was made through SPSS 6.1 software (SPSS, Chicago IL).…”

mentioning

confidence: 99%

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Association study of the G258S transferrin gene polymorphism and Parkinson's disease in the Spanish population

et al. 2005

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contrasting

confidence: 82%

mentioning

confidence: 99%

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Association study of the G258S transferrin gene polymorphism and Parkinson's disease in the Spanish population

et al. 2005

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“…Data from recent transcranial ultrasound studies also imply iron accumulation to occur very early in the disease process constituting rather a primary cause of the disease (Becker et al 1995;Berg et al 1999Berg et al , 2002). An association of sequence variations in some genes encoding for iron metabolizing proteins within the brain and PD has been established (Borie et al 2002;Hochstrasser et al 2004), while such an association could be ruled out in others (Felletschin et al 2003;Deplazes et al 2004). …”

Section: Ironmentioning

confidence: 95%

Redox imbalance

2004

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Substantial evidence implies that redox imbalance attributable to an overproduction of reactive oxygen species or reactive nitrogen species that overwhelm the protective defense mechanism of cells contributes to all forms of Parkinson's disease. Factors such as dopamine, neuromelanin, and transition metals may, under certain circumstances, contribute to the formation of oxygen species such as H(2)O(2), superoxide radicals, and hydroxyl radicals and react with reactive nitrogen species such as nitric oxide or peroxinitrite. Mitochodrial dysfunction and excitotoxicity may be a cause and a result of oxidative stress. Consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage, and interference of reactive oxygen species with signal transduction pathways. These consequences become even more harmful when genetic variations impair the normal degradation of altered proteins. Therefore, therapeutic strategies must aim at reducing free-radical formation and scavenging free-radicals.

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“…While on the one hand primary events like an association of sequence variations in some genes encoding for iron metabolizing proteins within the brain and PD (Borie et al, 2002, Hochstrasser et al, 2004 as well as a continuous and unlimitedly iron uptake through a disturbed blood brain-barrier are being disucussed as a reason for the elevated iron levels (Riederer, 2004;Kortekaas et al, 2005), others favour the hypothesis of secondary iron accumulation and enhanced OS in the course of neurodegeneration (Dawson and Dawson, 2003).…”

Section: Introductionmentioning

confidence: 96%

Disturbance of iron metabolism in Parkinson’s disease — ultrasonography as a biomarker

et al. 2006

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A central role of iron in the pathogenesis of Parkinson's disease (PD) has been discussed for many years. So far, however, a biomarker indicating increased iron levels in the substantia nigra (SN) in PD patients has been missing. Performing transcranial ultrasound we detected an increased area of SN echogenicity as a typical echofeature in PD, visible already in the early stages of the disease and in subjects with subclinical impairment of the nigrostriatal system. Animal studies and post mortem analyses of human brain tissue revealed that this echofeature is associated with increased iron levels of the substantia nigra as well as a reduced neuromelanin content. The apparently autosomal dominant inheritance of this echofeature in relatives of patients with idiopathic PD indicates a primary role of disturbances of iron metabolism in PD. Consequently performed mutation analyses in genes involved in brain iron metabolism lead to the discovery of specific mutations in the ferritin-H, IRP2 and HFE gene in single PD patients. Moreover, variations in the ceruloplasmin gene were found to be associated with PD or SN hyperechogenicity. Functional relevance of some of these mutations for iron metabolism could be proven. Therefore, SN hyperechogenicity can be regarded as biomarker for both: impairment of the nigrostriatal system and increased iron levels of the SN. Future studies aim at substantiating the hypothesis that healthy subjects with SN hyperechogenicity indeed represent a population at risk for nigrostriatal degeneration, which would have a significant impact on therapeutical options.

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Association study between iron-related genes polymorphisms and Parkinson's disease

Cited by 104 publications

References 15 publications

Association study of the G258S transferrin gene polymorphism and Parkinson's disease in the Spanish population

Association study of the G258S transferrin gene polymorphism and Parkinson's disease in the Spanish population

Redox imbalance

Disturbance of iron metabolism in Parkinson’s disease — ultrasonography as a biomarker

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