GSK3β reduces risk of sporadic Parkinson's disease in ethnic Chinese.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.23). 07/2012; 159B(6):718-21. DOI: 10.1002/ajmg.b.32075
Source: PubMed

ABSTRACT Genetic variability of glycogen synthase kinase-3β (GSK3β) may be linked to Parkinson's disease (PD). Its role in ethnic Chinese population is still unclear. We examined the association between GSK3β variation and PD in a Han Chinese population from mainland China. Using a case-control methodology, we genotyped the single nucleotide polymorphism (SNP) in GSK3β (rs334558) to investigate the association with risk of PD. A total of 1,280 ethnic Han Chinese study subjects comprising 761 sporadic PD patients and 519 controls were recruited. The T allele of a promoter SNP rs334558 was found to reduce the risk of PD (OR = 0.82, 95% CI: 0.696-0.960, P = 0.014). Patients with CT + TT genotypes have a reduced risk of PD compared to those with CC genotype (OR = 0.61, 95% CI: 0.477-0.776, P = 6.09E-5). In addition, we demonstrated that CT + TT subjects cannot be distinguished from CC subjects based on their clinical features. Our data suggest that rs334558 variant in GSK3β reduces the risk of PD in a Han Chinese population from mainland China. Further studies of large series of subjects are necessary to fully elucidate the true role of GSK3β in PD.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson disease (PD) is the second most common form of neurodegeneration among elderly individuals. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. In this paper, we review the evidence for an association between PD and thiamine. Interestingly, a significant association has been demonstrated between PD and low levels of serum thiamine, and thiamine supplements appear to have beneficial clinical effects against PD. Multiple studies have evaluated the connection between thiamine and PD pathology, and candidate pathways involve the transcription factor Sp1, p53, Bcl-2, caspase-3, tyrosine hydroxylase, glycogen synthase kinase-3β, vascular endothelial growth factor, advanced glycation end products, nuclear factor kappa B, mitogen-activated protein kinase, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thus, a review of the literature suggests that thiamine plays a role in PD, although further investigation into the effects of thiamine in PD is needed.
    CNS Neuroscience & Therapeutics 03/2013; · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies on the association between glycogen synthase kinase 3 beta (GSK3-β) polymorphisms (rs334558 and rs6438552) and Parkinson's disease (PD) susceptibility remained inconsistent. Thus, the goal of this study was to re-examine their exact association by a meta-analysis. All eligible studies were identified by a systematic literature search of multiple databases. Six studies (3,105 cases and 4,387 controls) on rs334558 and six studies (2,579 cases and 4,091 controls) on rs6438552 were included. The quality of these studies was generally good according to the Newcastle-Ottawa Scale (NOS). The meta-analysis showed null association between the two variants and PD susceptibility in all genetic models from the overall or Caucasian population. However, the analysis of rs334558 revealed that the risk of PD decreased in heterozygote, dominant or additive models (OR=0.60, 95% CI: 0.48, 0.74; OR=0.63, 95% CI: 0.51, 0.78; OR=0.82, 95% CI: 0.71, 0.94, respectively) from the Eastern Asian population. Moreover, the analysis on the homozygote, heterozygote, dominant or additive models suggested that rs6438552 also reduced the PD risk (OR=0.45, 95% CI: 0.24, 0.84; OR=0.62, 95% CI: 0.39, 0.97; OR=0.57, 95% CI: 0.37, 0.87; OR=0.66, 95% CI: 0.49, 0.88, respectively) in the Eastern Asian population. Together, the findings suggest that the two variants both reduced the risk of PD in the Eastern Asian subgroup but not in the overall and Caucasian population, which should be cautiously interpreted because of limited number of included studies.
    Gene 04/2013; · 2.20 Impact Factor