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.
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.
Authors: M Martinez; A Brice; J R Vaughan; A Zimprich; M M B Breteler; G Meco; A Filla; M J Farrer; C Bétard; J Hardy; G De Michele; V Bonifati; B Oostra; T Gasser; N W Wood; A Dürr Journal: J Med Genet Date: 2004-12 Impact factor: 6.318
Authors: Jennifer E Tobin; Jing Cui; Jemma B Wilk; Jeanne C Latourelle; Jason M Laramie; Ann C McKee; Mark Guttman; Samer Karamohamed; Anita L DeStefano; Richard H Myers Journal: Brain Res Date: 2007-01-08 Impact factor: 3.252
Authors: M Sharma; J C Mueller; A Zimprich; P Lichtner; A Hofer; P Leitner; S Maass; D Berg; A Dürr; V Bonifati; G De Michele; B Oostra; A Brice; N W Wood; B Muller-Myhsok; T Gasser Journal: J Med Genet Date: 2006-01-27 Impact factor: 6.318
Authors: Sofia A Oliveira; Yi-Ju Li; Maher A Noureddine; Stephan Zuchner; Xuejun Qin; Margaret A Pericak-Vance; Jeffery M Vance Journal: Am J Hum Genet Date: 2005-06-28 Impact factor: 11.025
Authors: Seungkyoung Yang; Young Jae Lee; Jin-Man Kim; Sean Park; Joanna Peris; Philip Laipis; Young Shik Park; Jae Hoon Chung; S Paul Oh Journal: Am J Hum Genet Date: 2006-01-31 Impact factor: 11.025