Molecular Biology Reports

, Volume 41, Issue 4, pp 2307–2311 | Cite as

Genetic analysis of the ATP1B4 gene in Chinese Han patients with Parkinson’s disease

  • Kai Gao
  • Zhi Song
  • Hui Liang
  • Wen Zheng
  • Xiong Deng
  • Yi Yuan
  • Yongxiang Zhao
  • Hao Deng


Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity and postural instability. Mutations in the ATPase 13A2 gene were found to be the causes for the Kufor-Rakeb syndrome, a rare form of recessively inherited atypical juvenile parkinsonism. The ATPase Na+/K+ transporting beta 4 polypeptide gene (ATP1B4) is located within a 19-centimorgen region of the PARK12 near the marker DXS1001 and it encodes a protein named βm, a member of P-type ATPases β-subunit family. To determine whether mutations in the ATP1B4 gene are associated with PD, we screened the coding region of this gene in 100 Chinese Han patients with PD. A known single nucleotide variant rs2072452 (c.143T > C), predicted to lead to amino acid substitution (p.Val48Ala), was identified. Extended analysis of 202 patients with PD and 400 gender, age, and ethnicity matched healthy controls showed no significant differences between patients and control subjects for genotypic and allelic distributions (P = 0.638 for genotypic distribution; P = 0.685 for allelic distribution in females and P = 0.303 for allelic distribution in males), suggesting the variant in the coding region of the ATP1B4 gene may play little or no role in the development of PD in Chinese Han population.


Parkinson’s disease Chinese Han ATP1B4 Variant 



This work was supported by Research Fund for the Doctoral Program of Higher Education of China (20110162110026), National Natural Science Foundation of China (81101339, 81271921), Sheng Hua Scholars Program of Central South University, China (H.D.), Mittal Students Innovative Projects of Central South University, China (11MX28) and Grant for the Foster Key Subject of the Third Xiangya Hospital (Clinical Laboratory Diagnostics).

Conflict of interest

The authors report no conflicts of interest.


  1. 1.
    de Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5:525–535PubMedCrossRefGoogle Scholar
  2. 2.
    Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C et al (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 41:1303–1307PubMedCrossRefGoogle Scholar
  3. 3.
    Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214PubMedCrossRefGoogle Scholar
  4. 4.
    Lesage S, Brice A (2012) Role of Mendelian genes in “sporadic” Parkinson’s disease. Parkinsonism Relat Disord 18(Suppl 1):S66–S70PubMedCrossRefGoogle Scholar
  5. 5.
    Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D et al (2006) Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 38:1184–1191PubMedCrossRefGoogle Scholar
  6. 6.
    Di Fonzo A, Chien HF, Socal M, Giraudo S, Tassorelli C et al (2007) ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease. Neurology 68:1557–1562PubMedCrossRefGoogle Scholar
  7. 7.
    Lin CH, Tan EK, Chen ML, Tan LC, Lim HQ et al (2008) Novel ATP13A2 variant associated with Parkinson disease in Taiwan and Singapore. Neurology 71:1727–1732PubMedCrossRefGoogle Scholar
  8. 8.
    Chen CM, Lin CH, Juan HF, Hu FJ, Hsiao YC et al (2011) ATP13A2 variability in Taiwanese Parkinson’s disease. Am J Med Genet B 156B:720–729CrossRefGoogle Scholar
  9. 9.
    Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A et al (2002) Genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations. Am J Hum Genet 71:124–135PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Pankratz N, Nichols WC, Uniacke SK, Halter C, Murrell J et al (2003) Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families. Hum Mol Genet 12:2599–2608PubMedCrossRefGoogle Scholar
  11. 11.
    Deng H, Xu H, Deng X, Song Z, Zheng W et al (2012) VPS35 mutation in Chinese Han patients with late-onset Parkinson’s disease. Eur J Neurol 19:e96–e97PubMedCrossRefGoogle Scholar
  12. 12.
    Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376PubMedCrossRefGoogle Scholar
  13. 13.
    Lei J, Deng X, Zhang J, Su L, Xu H et al (2012) Mutation screening of the HDC gene in Chinese Han patients with Tourette syndrome. Am J Med Genet B 159B:72–76CrossRefGoogle Scholar
  14. 14.
    Williams DR, Hadeed A, Al-Din AS, Wreikat AL, Lees AJ (2005) Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Mov Disord 20:1264–1271PubMedCrossRefGoogle Scholar
  15. 15.
    Crosiers D, Ceulemans B, Meeus B, Nuytemans K, Pals P et al (2011) Juvenile dystonia-parkinsonism and dementia caused by a novel ATP13A2 frameshift mutation. Parkinsonism Relat Disord 17:135–138PubMedCrossRefGoogle Scholar
  16. 16.
    Djarmati A, Hagenah J, Reetz K, Winkler S, Behrens MI et al (2009) ATP13A2 variants in early-onset Parkinson’s disease patients and controls. Mov Disord 24:2104–2111PubMedCrossRefGoogle Scholar
  17. 17.
    Eiberg H, Hansen L, Korbo L, Nielsen IM, Svenstrup K et al (2011) Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9). Clin Genet 82:256–263PubMedCrossRefGoogle Scholar
  18. 18.
    Fong CY, Rolfs A, Schwarzbraun T, Klein C, O’Callaghan FJ (2011) Juvenile parkinsonism associated with heterozygous frameshift ATP13A2 gene mutation. Eur J Paediatr Neurol 15:271–275PubMedCrossRefGoogle Scholar
  19. 19.
    Ning YP, Kanai K, Tomiyama H, Li Y, Funayama M et al (2008) PARK9-linked parkinsonism in Eastern Asia: mutation detection in ATP13A2 and clinical phenotype. Neurology 70:1491–1493PubMedCrossRefGoogle Scholar
  20. 20.
    Paisan-Ruiz C, Guevara R, Federoff M, Hanagasi H, Sina F et al (2010) Early-onset l-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. Mov Disord 25:1791–1800PubMedCrossRefGoogle Scholar
  21. 21.
    Park JS, Mehta P, Cooper AA, Veivers D, Heimbach A et al (2011) Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism. Hum Mutat 32:956–964PubMedCrossRefGoogle Scholar
  22. 22.
    Santoro L, Breedveld GJ, Manganelli F, Iodice R, Pisciotta C et al (2011) Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability. Neurogenetics 12:33–39PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Ugolino J, Fang S, Kubisch C, Monteiro MJ (2011) Mutant Atp13a2 proteins involved in parkinsonism are degraded by ER-associated degradation and sensitize cells to ER-stress induced cell death. Hum Mol Genet 20:3565–3577PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Ramonet D, Podhajska A, Stafa K, Sonnay S, Trancikova A et al (2012) PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity. Hum Mol Genet 21:1725–1743PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Pestov NB, Zhao H, Basrur V, Modyanov NN (2011) Isolation and characterization of BetaM protein encoded by ATP1B4—a unique member of the Na, K-ATPase beta-subunit gene family. Biochem Biophys Res Commun 412:543–548PubMedCrossRefGoogle Scholar
  26. 26.
    Zhao H, Pestov NB, Korneenko TV, Shakhparonov MI, Modyanov NN (2004) Accumulation of beta (m), a structural member of X, K-ATPase beta-subunit family, in nuclear envelopes of perinatal myocytes. Am J Physiol Cell Physiol 286:C757–C767PubMedCrossRefGoogle Scholar
  27. 27.
    Pestov NB, Ahmad N, Korneenko TV, Zhao H, Radkov R et al (2007) Evolution of Na, K-ATPase beta m-subunit into a coregulator of transcription in placental mammals. Proc Natl Acad Sci USA 104:11215–11220PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Palmgren MG, Nissen P (2011) P-type ATPases. Annu Rev Biophys 40:243–266PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Kai Gao
    • 1
  • Zhi Song
    • 2
  • Hui Liang
    • 1
  • Wen Zheng
    • 2
  • Xiong Deng
    • 1
  • Yi Yuan
    • 1
  • Yongxiang Zhao
    • 3
  • Hao Deng
    • 1
    • 2
  1. 1.Center for Experimental Medicine, The Third Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of Neurology, The Third Xiangya HospitalCentral South UniversityChangshaChina
  3. 3.Department of Cardiothoracic Surgery, The First Affiliated HospitalGuangxi Medical UniversityNanningChina

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