PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups

Katarzyna Gaweda-Walerych, Krzysztof Safranow, Barbara Jasinska-Myga, Monika Bialecka, Gabriela Klodowska-Duda, Monika Rudzinska, Krzysztof Czyzewski, Stephanie A. Cobb, Jaroslaw Slawek, Maria Styczynska, Grzegorz Opala, Marek Drozdzik, Kenya Nishioka, Matthew J. Farrer, Owen A Ross, Zbigniew K Wszolek, Maria Barcikowska, Cezary Zekanowski

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aims and objectives: A new pathomechanism of Parkinson's disease (PD) involving regulation of mitochondrial functions was recently proposed. Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, which is abolished by PARK2 gene mutations. We have previously shown that mitochondrial haplogroups/clusters and TFAM common variation influenced PD risk. We investigate the role of PARK2 polymorphisms on PD risk and their interactions with mitochondrial haplogroups/clusters as well as with TFAM variability. Methods: 104 early-onset PD patients (EOPD, age at onset ≤50 years) were screened for PARK2 coding sequence changes including gene dosage alterations. Three selected PARK2 polymorphisms (S167N, V380L, D394N) were genotyped in 326 PD patients and 315 controls using TaqMan allelic discrimination assay. Results: PARK2 screen revealed two heterozygous changes in two EOPD patients: exon 2 deletion and one novel synonymous variation (c.999C > A, P333P).In association study no differences in genotype/allele frequencies of S167N, V380L, D394N were found between analyzed groups. Stratification by mitochondrial clusters revealed higher frequency of V380L G/G genotype and allele G in PD patients, within HV cluster (p = 0.040; p = 0.022, respectively). Moreover, interaction between genotypes G/G V380L of PARK2 and G/G rs2306604 of TFAM, within HV cluster was significant (OR 2.05; CI 1.04-4.04; p = 0.038). Conclusions: Our results indicate that co-occurrence of G/G V380L PARK2 and G/G rs2306604 TFAM on the prooxidative HV cluster background can contribute to PD risk. We confirm low PARK2 mutation frequency in Polish EOPD patients.

Original languageEnglish (US)
Pages (from-to)520-524
Number of pages5
JournalParkinsonism and Related Disorders
Volume18
Issue number5
DOIs
StatePublished - Jun 2012

Fingerprint

Parkinson Disease
Genotype
Gene Dosage
Organelle Biogenesis
Mutation Rate
Mitochondrial DNA
Age of Onset
Gene Frequency
Exons
Alleles
Mutation
Genes

Keywords

  • Mitochondrial clusters
  • Mitochondrial transcription factor A (TFAM)
  • PARK2
  • Parkinson's disease risk factors

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Gaweda-Walerych, K., Safranow, K., Jasinska-Myga, B., Bialecka, M., Klodowska-Duda, G., Rudzinska, M., ... Zekanowski, C. (2012). PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups. Parkinsonism and Related Disorders, 18(5), 520-524. https://doi.org/10.1016/j.parkreldis.2012.01.021

PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups. / Gaweda-Walerych, Katarzyna; Safranow, Krzysztof; Jasinska-Myga, Barbara; Bialecka, Monika; Klodowska-Duda, Gabriela; Rudzinska, Monika; Czyzewski, Krzysztof; Cobb, Stephanie A.; Slawek, Jaroslaw; Styczynska, Maria; Opala, Grzegorz; Drozdzik, Marek; Nishioka, Kenya; Farrer, Matthew J.; Ross, Owen A; Wszolek, Zbigniew K; Barcikowska, Maria; Zekanowski, Cezary.

In: Parkinsonism and Related Disorders, Vol. 18, No. 5, 06.2012, p. 520-524.

Research output: Contribution to journalArticle

Gaweda-Walerych, K, Safranow, K, Jasinska-Myga, B, Bialecka, M, Klodowska-Duda, G, Rudzinska, M, Czyzewski, K, Cobb, SA, Slawek, J, Styczynska, M, Opala, G, Drozdzik, M, Nishioka, K, Farrer, MJ, Ross, OA, Wszolek, ZK, Barcikowska, M & Zekanowski, C 2012, 'PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups', Parkinsonism and Related Disorders, vol. 18, no. 5, pp. 520-524. https://doi.org/10.1016/j.parkreldis.2012.01.021
Gaweda-Walerych K, Safranow K, Jasinska-Myga B, Bialecka M, Klodowska-Duda G, Rudzinska M et al. PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups. Parkinsonism and Related Disorders. 2012 Jun;18(5):520-524. https://doi.org/10.1016/j.parkreldis.2012.01.021
Gaweda-Walerych, Katarzyna ; Safranow, Krzysztof ; Jasinska-Myga, Barbara ; Bialecka, Monika ; Klodowska-Duda, Gabriela ; Rudzinska, Monika ; Czyzewski, Krzysztof ; Cobb, Stephanie A. ; Slawek, Jaroslaw ; Styczynska, Maria ; Opala, Grzegorz ; Drozdzik, Marek ; Nishioka, Kenya ; Farrer, Matthew J. ; Ross, Owen A ; Wszolek, Zbigniew K ; Barcikowska, Maria ; Zekanowski, Cezary. / PARK2 variability in Polish Parkinson's disease patients - interaction with mitochondrial haplogroups. In: Parkinsonism and Related Disorders. 2012 ; Vol. 18, No. 5. pp. 520-524.
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abstract = "Aims and objectives: A new pathomechanism of Parkinson's disease (PD) involving regulation of mitochondrial functions was recently proposed. Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, which is abolished by PARK2 gene mutations. We have previously shown that mitochondrial haplogroups/clusters and TFAM common variation influenced PD risk. We investigate the role of PARK2 polymorphisms on PD risk and their interactions with mitochondrial haplogroups/clusters as well as with TFAM variability. Methods: 104 early-onset PD patients (EOPD, age at onset ≤50 years) were screened for PARK2 coding sequence changes including gene dosage alterations. Three selected PARK2 polymorphisms (S167N, V380L, D394N) were genotyped in 326 PD patients and 315 controls using TaqMan allelic discrimination assay. Results: PARK2 screen revealed two heterozygous changes in two EOPD patients: exon 2 deletion and one novel synonymous variation (c.999C > A, P333P).In association study no differences in genotype/allele frequencies of S167N, V380L, D394N were found between analyzed groups. Stratification by mitochondrial clusters revealed higher frequency of V380L G/G genotype and allele G in PD patients, within HV cluster (p = 0.040; p = 0.022, respectively). Moreover, interaction between genotypes G/G V380L of PARK2 and G/G rs2306604 of TFAM, within HV cluster was significant (OR 2.05; CI 1.04-4.04; p = 0.038). Conclusions: Our results indicate that co-occurrence of G/G V380L PARK2 and G/G rs2306604 TFAM on the prooxidative HV cluster background can contribute to PD risk. We confirm low PARK2 mutation frequency in Polish EOPD patients.",
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AU - Safranow, Krzysztof

AU - Jasinska-Myga, Barbara

AU - Bialecka, Monika

AU - Klodowska-Duda, Gabriela

AU - Rudzinska, Monika

AU - Czyzewski, Krzysztof

AU - Cobb, Stephanie A.

AU - Slawek, Jaroslaw

AU - Styczynska, Maria

AU - Opala, Grzegorz

AU - Drozdzik, Marek

AU - Nishioka, Kenya

AU - Farrer, Matthew J.

AU - Ross, Owen A

AU - Wszolek, Zbigniew K

AU - Barcikowska, Maria

AU - Zekanowski, Cezary

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