Association studies of multiple candidate genes for Parkinson's Disease using single nucleotide polymorphisms

Momose, Yoshika; Murata, Miho; Kobayashi, Kenzo; Tachikawa, Masaji; Nakabayashi, Yasuo; Kanazawa, Ichiro; Toda, Tatsushi

doi:10.1002/ana.1305

Cited by 52 publications

(73 citation statements)

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“…Consistent with this, lower episodic memory scores (on the Wechsler memory scale) have been seen in both normal controls and schizophrenia patients with met alleles, together with abnormal hippocampal activation on fMRI [6,16]. However the impact of BDNF polymorphisms on cognitive processes among PD patients has not been explored, as previous studies with BDNF in PD have only looked for the relationship between polymorphisms and for the risk for developing the disease [14,18,26,29].…”

Section: Introductionmentioning

confidence: 84%

The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

et al. 2005

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Parkinson's disease (PD) patients show a range of cognitive deficits,which may relate to abnormalities in dopaminergic transmission in fronto-striatal circuitry. In this study, we have investigated the impact of brainderived neurotrophic factor (BDNF) val66met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population-based study of PD were genotyped for the BDNF val66met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson's disease.

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Section: Introductionmentioning

confidence: 84%

The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

et al. 2005

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“…On the other hand, a common polymorphism (Ser18Tyr) has been frequently observed in various races. The Ser18Tyr is associated with decreased risk of PD and it is known that the protective effect is dose-dependent [68,69].…”

Section: Park5 (Uch-l1)mentioning

confidence: 99%

Familial Parkinson?s disease: a hint to elucidate the mechanisms of nigral degeneration

Kobayashi

Sasaki-Hatano

Sato

et al. 2003

Journal of Neurology

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In the majority of patients with Parkinson's disease (PD), it is now clear that genetic factors contribute to the pathogenesis of PD, although the contribution of genetic and environmental factors remains to be elucidated. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies, and the existence of familial PD based on single gene defects. Recently, several genes have been mapped and identified in patients with familial PD (FPD). alpha-Synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features and Lewy body positive pathology. In contrast, parkin is responsible for autosomal recessive form of earlyonset PD with Lewy body-negative pathology. This form is identified with world-wide distribution among patients with young-onset PD. Furthermore, ubiquitin carboxy terminal hydrolase L1 (UCHL1) gene is responsible for an autosomal dominant form of typical PD, although only a single family has so far been identified with a mutation of this gene. In addition, DJ-1 has been identified as a causative gene for PARK7, a recessive form of familial PD. Now, a total of five causative genes including NR4A2 have been identified, and others such as PARK3, -4, -6, -8, -9, -10 have been mapped as hereditary forms of familial PD. The presence of different loci or different causative genes indicates that PD is not a single entity but a highly heterogeneous disorder. However, the functions of causative genes may share a common pathway such as an ubiquitin-proteasome pathway. Thus, identification and elucidation of the causative genes should enhance our understanding of the pathogenesis of not only familial PD, but also sporadic PD.

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“…Subsequent screening of this gene has consistently been negative, suggesting that I93M is either a rare cause of PD or a rare neutral polymorphism [61][62][63][64]. Involvement of UCHL1 in the pathogenesis of PD is also supported by the fact that a different polymorphism in this gene (S18Y) seems inversely associated with PD [65][66][67][68], and that the UCHL1 protein displays ubiquitin ligase activity for a-synuclein in vitro [69]. Although the genetic evidence is not entirely convincing, the function of UCHL1 makes it likely that this protein is involved in the pathogenesis of PD.…”

Section: Park5/ubiquitin C-terminal Hydrolase-l1 (Uchl1)mentioning

confidence: 98%

Unraveling the pathogenesis of Parkinson?s disease ? the contribution of monogenic forms

Bonifati

Oostra

Heutink

2004

CMLS, Cell. Mol. Life Sci.

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The field of Parkinson's disease pathogenesis is rapidly evolving from the one of a monolithic and obscure entity into the one of a complex scenario with several known molecular players. The ongoing systematic exploration of the genome holds great promise for the identification of the genetic factors conferring susceptibility to the common non-Mendelian forms of this disease. However, most of the progress of the last 5 years has come from the successful mapping and cloning of genes responsible for rare Mendelian variants of Parkinson's disease. These discoveries are providing tremendous help in understanding the molecular mechanisms of this devastating disease. Here we review the genetics of the monogenic forms of Parkinson's disease. Moreover, we focus on the mechanisms of disease caused by alpha-synuclein and parkin mutations, and the implications of this growing body of knowledge for understanding the pathogenesis of the common forms of the disease.

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Association studies of multiple candidate genes for Parkinson's Disease using single nucleotide polymorphisms

Cited by 52 publications

References 1 publication

The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

Familial Parkinson?s disease: a hint to elucidate the mechanisms of nigral degeneration

Unraveling the pathogenesis of Parkinson?s disease ? the contribution of monogenic forms

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