Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease

Hochstrasser, Helmine; Bauer, Peter; Walter, Uwe; Behnke, Stefanie; Spiegel, Jörg; Csóti, Ilona; Zeiler, Björn; Bornemann, Antje; Pahnke, Jens; Becker, Georg; Rieß, Olaf; Berg, Daniela

doi:10.1212/01.wnl.0000144276.29988.c3

Cited by 109 publications

(101 citation statements)

References 34 publications

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“…In this study, five unique missense variations were identified including, a single incidence of I63T, D554E, which correlated with PD and positive ultrasound for increased substantia nigra iron levels, and R793H, which was linked to increased levels of iron levels in individuals with PD and their age/ethnic-matched individuals. This study also showed that Cp localizes with the Lewy bodies associated with the pathology of PD (134). In further investigation, the I63T mutant Cp isoform was expressed at half the normal level and displayed a distinct decrease in ferroxidase activity in vivo.…”

Section: Iron Regulation and Neurodegenerationsupporting

confidence: 58%

“…A study of 176 individuals with PD and 180 control subjects who underwent transcranial ultrasound to reveal elevated substantia nigra iron levels, subsequently were evaluated for mutations in the Cp gene (134). In this study, five unique missense variations were identified including, a single incidence of I63T, D554E, which correlated with PD and positive ultrasound for increased substantia nigra iron levels, and R793H, which was linked to increased levels of iron levels in individuals with PD and their age/ethnic-matched individuals.…”

Section: Iron Regulation and Neurodegenerationmentioning

confidence: 99%

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Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications

Mackenzie

Iwasaki

Tsuji

2008

Antioxidants & Redox Signaling

440

372

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Section: Iron Regulation and Neurodegenerationsupporting

confidence: 58%

Section: Iron Regulation and Neurodegenerationmentioning

confidence: 99%

Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications

Mackenzie

Iwasaki

Tsuji

2008

Antioxidants & Redox Signaling

440

372

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“…However, less is known about the cause of low serum CP levels in PD patients. In this study, we found that the CP gene in The frequency of D544E differed significantly between PD patients and controls [24] . Another study by Castiglioni CP gene variants seemed to be associated with PD in this study [25] .…”

Section: No Copy Number Variations Of the Cp Gene In Pd Patientsmentioning

confidence: 52%

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson’s disease

et al. 2015

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Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were signifi cantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no signifi cant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

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“…Increased echogenicity of SNc can be documented in 90% of PD patients by transcranial ultrasound, suggestive of iron accumulation [8]. PD patients with Cp missense mutations were found to have reduced Cp levels and ferroxidase activity [9].…”

Section: Discussionmentioning

confidence: 99%

Reduced Serum Caeruloplasmin Levels in Non-Wilsonian Movement Disorders

Ling

Bhidayasiri²

2011

Eur Neurol

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Reduction in caeruloplasmin (Cp) levels is sometimes found in other sporadic movement disorders, not limited to Wilson’s disease (WD). Serum levels of Cp, copper, iron and gamma-glutamyl transpeptidase were measured in 71 patients with various diagnoses of movement disorders, including Parkinson’s disease (PD), atypical parkinsonian disorders, tardive dyskinesia, essential tremor, and idiopathic focal dystonia, and compared with those of 26 healthy age- and gender-matched controls. The mean Cp level in the patient group was 20.5 ± 4.2 mg/dl , lower than in controls (23.5 ± 7.2 mg/dl; p = 0.005). In subgroup analysis, mean Cp level of PD patients (19.6 ± 3.0 mg/dl) was lower than that of controls (p = 0.045). In a group analysis as neurodegenerative movement disorders (NDD), their mean Cp level was 19.9 ± 3.0 mg/dl, lower than that of controls (p = 0.019). Linear regression analysis indicated that the presence of NDD was the main factor associated with lower Cp levels. The finding of reduced serum Cp level in non-Wilsonian movement disorders and selective reduction in the neurodegenerative subgroup supports the notion that Cp might be associated with the cascade of neurotoxicity in NDD. The variation in Cp level in other non-WD conditions highlights the fact that Cp level is a poor screening test for WD in the absence of clear clinical suspicion.

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Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease

Cited by 109 publications

References 34 publications

Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications

Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson’s disease

Reduced Serum Caeruloplasmin Levels in Non-Wilsonian Movement Disorders

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