title: Association between AKT1 gene and Parkinson's disease: a protective haplotype.
abstract: Variation in AKT1 has been associated with schizophrenia, bipolar disease and type II diabetes. The aim of the present study was to investigate the potential role of variability within AKT1 as a risk factor for Parkinson's disease (PD). We performed a case-control association analysis of AKT1 in a Greek cohort of PD using four tagging SNPs and five constructed haplotypes. To assess the structure of this locus in different populations we have performed linkage disequilibrium (LD) analysis using these variants [dunning]. In multilocus analysis, the frequency of a four-SNP1/2/3/4 haplotype was significantly higher in controls in comparison with PD patients (chi(2)=19.76, p=0.00009, OR=0.11 C.I.=0.03-0.35). The association remained significant even after Bonferroni correction for the number of haplotypes (p=0.0002). So, this certain haplotype was significantly associated with reduced risk of the disease. The data presented here suggest the involvement of AKT1 in protection of PD through many possible mechanisms involving different signaling pathways that could be potential therapeutic targets in the future.
authors.affiliation: University of Thessaly, Medical School, Department of Neurology, Neurogenetics Unit, Papakyriazi 22 Street, Larissa 41222, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Xiromerisiou
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Katsarogiannis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gourbali
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt