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Original article

Vol. 142 No. 0910 (2012)

A novel synonymous SNP in PITX3 is associated with Parkinson’s disease in a Chinese population

  • Yaxing Gui
  • Yijia Zhao
  • Hai Liu
  • Jiang Fu
  • Zhongping Xu
  • Xingyue Hu
DOI
https://doi.org/10.4414/smw.2012.13521
Cite this as:
Swiss Med Wkly. 2012;142:w13521
Published
26.02.2012

Summary

BACKGROUND AND PURPOSE: Paired-like homeodomain transcription factor 3 (PITX3) is an important transcription factor for differentiation and survival of dopaminergic neurons. Recent reports have shown a strong association of polymorphisms in the PITX3 gene with Parkinson’s disease (PD). Our study was designed to verify whether three previous PITX3 SNPs (rs2281983, rs4919621 and rs3758549) were associated with PD in the Chinese population. We also investigate the association of novel polymorphisms in PITX3 gene with PD.

METHODS: All the polymorphisms of PITX3 we found in this study were sequenced by PCR products from both directions with dye terminator methods using an ABI-3100 sequencer. We included 356 sporadic PD patients and 300 healthy elderly people as controls.

RESULTS: We provide evidence for strong association of a novel polymorphism c.219G>A (p = 0.000307) with PD. Our data showed that the substitution of c.219G>A in PITX3 Exon 3 was significantly higher in PD compared with control. Previous finding suggesting three SNPs (rs2281983, rs4919621 and rs3758549) in the PITX3 gene to be associated with PD could not be replicated.

CONCLUSIONS: Our findings indicate that a novel synonymous SNP in PITX3 gene may contribute to PD risk in the Chinese population.

References

  1. Smidt MP, Smits SM, Bouwmeester H, Hamers FP, van der Linden AJ, Hellemons AJ, et al. Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development. 2004;131:1145–55.
  2. Nunes I, Tovmasian LT, Silva RM, Burke RE, Goff SP. Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci. U S A 2003;100:4245–50.
  3. Smits SM, Smidt MP. The role of Pitx3 in survival of midbrain dopaminergic neurons. J Neural Transm Suppl. 2006:57–60.
  4. Hwang DY, Ardayfio P, Kang UJ, Semina EV, Kim KS. Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Brain Res Mol Brain Res. 2003;114:123–31.
  5. Fuchs J, Mueller JC, Lichtner P, Schulte C, Munz M, Berg D, et al. The transcription factor PITX3 is associated with sporadic Parkinson’s disease. Neurobiol Aging. 2007;30:731–8.
  6. Le W, Nguyen D, Lin XW, Rawal P, Huang M, Ding Y, et al. Transcription factor PITX3 gene in Parkinson’s disease. Neurobiol Aging. 2011;32:750–3.
  7. Li J, Dani JA, Le W. The role of transcription factor Pitx3 in dopamine neuron development and Parkinson’s disease. Curr Top Med Chem. 2009;9:855–9.
  8. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13(Suppl 3):2–23.
  9. Le Pen G, Sonnier L, Hartmann A, Bizot JC, Trovero F, Krebs MO, et al. Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1: a new genetic model for Parkinson’s disease? Parkinsonism Relat Disord. 2008;14(Suppl 2):S107–111.
  10. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP. A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci. 2000;3:337–41.
  11. Schilter KF, Schneider A, Bardakjian T, Soucy JF, Tyler RC, Reis LM, et al. OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype. Clin Genet. 2011;79(2):158–68.
  12. Bergman O, Hakansson A, Westberg L, Nordenström K, Carmine Belin A, Sydow O, et al. PITX3 polymorphism is associated with early onset Parkinson’s disease. Neurobiol Aging. 2010; 31:114–7.
  13. Haubenberger D, Reinthaler E, Mueller JC, Pirker W, Katzenschlager R, Froehlich R, et al. Association of transcription factor polymorphisms PITX3 and EN1 with Parkinson’s disease. Neurobiol Aging. 2011;32:302–7.
  14. Thi Tran HT, Takeshima Y, Surono A, Yagi M, Wada H, Matsuo M. A G-to-A transition at the fifth position of intron-32 of the dystrophin gene inactivates a splice-donor site both in vivo and in vitro. Mol Genet Metab. 2005;85:213–9.
  15. Komar AA. Genetics. SNPs, silent but not invisible. Science. 2007;315:466–7.
  16. Yu LH, Lin ZF, Liu Y, Hu FY, He XH, Liu ZL, et al. The transcription factor Pitx3 is a risk modifier for Parkinson’s disease in a Chinese Han population. Eur J Neurol. 2011;18(5):778–83.
  17. Liu J, Sun QY, Tang BS, Hu L, Yu RH, Wang L, et al. PITX3 gene polymorphism is associated with Parkinson’s disease in Chinese population. Brain Res. 2011;1392:116–20.
  18. Cai Y, Ding H, Gu Z, Ma J, Chan P. Genetic variants of the PITX3 gene are not associated with late-onset sporadic Parkinson’s disease in a Chinese population. Neurosci Lett. 2011;498(2):124–6.