The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

Chin Song Lu, Yah Huei Wu-Chou, Marina Van Doeselaar, Erik J. Simons, Hsiu Chen Chang, Guido J. Breedveld, Alessio Di Fonzo, Rou Shayn Chen, Yi Hsin Weng, Szu Chia Lai, Ben A. Oostra, Vincenzo Bonifati

Research output: Contribution to journalArticle

Abstract

The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4%) and Gly2385Arg variants (PAR ∼6%) yields a total PAR of ∼10%.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalNeurogenetics
Volume9
Issue number4
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Leucine
Parkinson Disease
Phosphotransferases
Population
Haplotypes
Founder Effect
Taiwan
Age of Onset
Referral and Consultation
Alleles
Proteins

Keywords

  • Association
  • Genetics
  • LRRK2
  • Parkinson's disease
  • Risk allele

ASJC Scopus subject areas

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Genetics

Cite this

Lu, C. S., Wu-Chou, Y. H., Van Doeselaar, M., Simons, E. J., Chang, H. C., Breedveld, G. J., ... Bonifati, V. (2008). The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population. Neurogenetics, 9(4), 271-276. https://doi.org/10.1007/s10048-008-0140-6

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population. / Lu, Chin Song; Wu-Chou, Yah Huei; Van Doeselaar, Marina; Simons, Erik J.; Chang, Hsiu Chen; Breedveld, Guido J.; Di Fonzo, Alessio; Chen, Rou Shayn; Weng, Yi Hsin; Lai, Szu Chia; Oostra, Ben A.; Bonifati, Vincenzo.

In: Neurogenetics, Vol. 9, No. 4, 10.2008, p. 271-276.

Research output: Contribution to journalArticle

Lu, CS, Wu-Chou, YH, Van Doeselaar, M, Simons, EJ, Chang, HC, Breedveld, GJ, Di Fonzo, A, Chen, RS, Weng, YH, Lai, SC, Oostra, BA & Bonifati, V 2008, 'The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population', Neurogenetics, vol. 9, no. 4, pp. 271-276. https://doi.org/10.1007/s10048-008-0140-6
Lu CS, Wu-Chou YH, Van Doeselaar M, Simons EJ, Chang HC, Breedveld GJ et al. The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population. Neurogenetics. 2008 Oct;9(4):271-276. https://doi.org/10.1007/s10048-008-0140-6
Lu, Chin Song ; Wu-Chou, Yah Huei ; Van Doeselaar, Marina ; Simons, Erik J. ; Chang, Hsiu Chen ; Breedveld, Guido J. ; Di Fonzo, Alessio ; Chen, Rou Shayn ; Weng, Yi Hsin ; Lai, Szu Chia ; Oostra, Ben A. ; Bonifati, Vincenzo. / The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population. In: Neurogenetics. 2008 ; Vol. 9, No. 4. pp. 271-276.
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abstract = "The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8{\%}) than among controls (1.8{\%}; p = 0.004, OR 2.13, 95{\%} CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4{\%}) and Gly2385Arg variants (PAR ∼6{\%}) yields a total PAR of ∼10{\%}.",
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AU - Chang, Hsiu Chen

AU - Breedveld, Guido J.

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