A haplotype at the PARK3 locus influences onset age for Parkinson's disease: The GenePD study

Samer Karamohamed, A. L. DeStefano, J. B. Wilk, C. M. Shoemaker, L. I. Golbe, M. H. Mark, A. M. Lazzarini, O. Suchowersky, N. Labelle, M. Guttman, L. J. Currie, G. F. Wooten, M. Stacy, M. Saint-Hilaire, R. G. Feldman, K. M. Sullivan, G. Xu, R. Watts, J. Growdon, M. LewC. Waters, P. Vieregge, P. P. Pramstaller, C. Klein, B. A. Racette, J. S. Perlmutter, A. Parsian, Carlos Singer, E. Montgomery, K. Baker, J. F. Gusella, S. J. Fink, R. H. Myers, A. Herbert

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Abstract

Objective: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. Methods: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. Results: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). Conclusions: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

Original languageEnglish
Pages (from-to)1557-1561
Number of pages5
JournalNeurology
Volume61
Issue number11
StatePublished - Dec 9 2003

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Age of Onset
Haplotypes
Parkinson Disease
sepiapterin reductase
Single Nucleotide Polymorphism
Genes
Alleles
Homozygote
Dopamine
Chromosomes
Genotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Karamohamed, S., DeStefano, A. L., Wilk, J. B., Shoemaker, C. M., Golbe, L. I., Mark, M. H., ... Herbert, A. (2003). A haplotype at the PARK3 locus influences onset age for Parkinson's disease: The GenePD study. Neurology, 61(11), 1557-1561.

A haplotype at the PARK3 locus influences onset age for Parkinson's disease : The GenePD study. / Karamohamed, Samer; DeStefano, A. L.; Wilk, J. B.; Shoemaker, C. M.; Golbe, L. I.; Mark, M. H.; Lazzarini, A. M.; Suchowersky, O.; Labelle, N.; Guttman, M.; Currie, L. J.; Wooten, G. F.; Stacy, M.; Saint-Hilaire, M.; Feldman, R. G.; Sullivan, K. M.; Xu, G.; Watts, R.; Growdon, J.; Lew, M.; Waters, C.; Vieregge, P.; Pramstaller, P. P.; Klein, C.; Racette, B. A.; Perlmutter, J. S.; Parsian, A.; Singer, Carlos; Montgomery, E.; Baker, K.; Gusella, J. F.; Fink, S. J.; Myers, R. H.; Herbert, A.

In: Neurology, Vol. 61, No. 11, 09.12.2003, p. 1557-1561.

Research output: Contribution to journalArticle

Karamohamed, S, DeStefano, AL, Wilk, JB, Shoemaker, CM, Golbe, LI, Mark, MH, Lazzarini, AM, Suchowersky, O, Labelle, N, Guttman, M, Currie, LJ, Wooten, GF, Stacy, M, Saint-Hilaire, M, Feldman, RG, Sullivan, KM, Xu, G, Watts, R, Growdon, J, Lew, M, Waters, C, Vieregge, P, Pramstaller, PP, Klein, C, Racette, BA, Perlmutter, JS, Parsian, A, Singer, C, Montgomery, E, Baker, K, Gusella, JF, Fink, SJ, Myers, RH & Herbert, A 2003, 'A haplotype at the PARK3 locus influences onset age for Parkinson's disease: The GenePD study', Neurology, vol. 61, no. 11, pp. 1557-1561.
Karamohamed S, DeStefano AL, Wilk JB, Shoemaker CM, Golbe LI, Mark MH et al. A haplotype at the PARK3 locus influences onset age for Parkinson's disease: The GenePD study. Neurology. 2003 Dec 9;61(11):1557-1561.
Karamohamed, Samer ; DeStefano, A. L. ; Wilk, J. B. ; Shoemaker, C. M. ; Golbe, L. I. ; Mark, M. H. ; Lazzarini, A. M. ; Suchowersky, O. ; Labelle, N. ; Guttman, M. ; Currie, L. J. ; Wooten, G. F. ; Stacy, M. ; Saint-Hilaire, M. ; Feldman, R. G. ; Sullivan, K. M. ; Xu, G. ; Watts, R. ; Growdon, J. ; Lew, M. ; Waters, C. ; Vieregge, P. ; Pramstaller, P. P. ; Klein, C. ; Racette, B. A. ; Perlmutter, J. S. ; Parsian, A. ; Singer, Carlos ; Montgomery, E. ; Baker, K. ; Gusella, J. F. ; Fink, S. J. ; Myers, R. H. ; Herbert, A. / A haplotype at the PARK3 locus influences onset age for Parkinson's disease : The GenePD study. In: Neurology. 2003 ; Vol. 61, No. 11. pp. 1557-1561.
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abstract = "Objective: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. Methods: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. Results: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). Conclusions: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.",
author = "Samer Karamohamed and DeStefano, {A. L.} and Wilk, {J. B.} and Shoemaker, {C. M.} and Golbe, {L. I.} and Mark, {M. H.} and Lazzarini, {A. M.} and O. Suchowersky and N. Labelle and M. Guttman and Currie, {L. J.} and Wooten, {G. F.} and M. Stacy and M. Saint-Hilaire and Feldman, {R. G.} and Sullivan, {K. M.} and G. Xu and R. Watts and J. Growdon and M. Lew and C. Waters and P. Vieregge and Pramstaller, {P. P.} and C. Klein and Racette, {B. A.} and Perlmutter, {J. S.} and A. Parsian and Carlos Singer and E. Montgomery and K. Baker and Gusella, {J. F.} and Fink, {S. J.} and Myers, {R. H.} and A. Herbert",
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TY - JOUR

T1 - A haplotype at the PARK3 locus influences onset age for Parkinson's disease

T2 - The GenePD study

AU - Karamohamed, Samer

AU - DeStefano, A. L.

AU - Wilk, J. B.

AU - Shoemaker, C. M.

AU - Golbe, L. I.

AU - Mark, M. H.

AU - Lazzarini, A. M.

AU - Suchowersky, O.

AU - Labelle, N.

AU - Guttman, M.

AU - Currie, L. J.

AU - Wooten, G. F.

AU - Stacy, M.

AU - Saint-Hilaire, M.

AU - Feldman, R. G.

AU - Sullivan, K. M.

AU - Xu, G.

AU - Watts, R.

AU - Growdon, J.

AU - Lew, M.

AU - Waters, C.

AU - Vieregge, P.

AU - Pramstaller, P. P.

AU - Klein, C.

AU - Racette, B. A.

AU - Perlmutter, J. S.

AU - Parsian, A.

AU - Singer, Carlos

AU - Montgomery, E.

AU - Baker, K.

AU - Gusella, J. F.

AU - Fink, S. J.

AU - Myers, R. H.

AU - Herbert, A.

PY - 2003/12/9

Y1 - 2003/12/9

N2 - Objective: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. Methods: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. Results: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). Conclusions: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

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