Tags

Type your tag names separated by a space and hit enter

β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease.
Mol Genet Metab 2011 Sep-Oct; 104(1-2):149-52MG

Abstract

An increasing number of clinical, neuropathological and experimental evidence linking Gaucher disease and a spectrum of synucleinopathies, including Parkinson's disease (PD) has emerged over the last decade. In particular, several studies, despite individual differences, have shown that mutations in the β-glucocerebrosidase gene (GBA) are a risk factor for PD. Recently a study from Northern Greece has shown a significant overrepresentation of such mutations only in patients with early onset PD. In the present study 8 different GBA mutations covering 87% of the mutations identified in Gaucher disease patients diagnosed in Greece were investigated in two ethnic Greek cohorts of patients with sporadic Parkinson's disease. Cohort A included patients residing and originating from Thessaly, Central Greece (n=100) and cohort B included patients residing and/or originating from the greater area of Athens (n=105). Age-gender-ethnicity matched healthy individuals from the same areas were included as controls (n=206). In patients of cohort A 11 carriers of GBA mutations were identified (5/11:N370S, 2/11:L444P, 2/11: D409H;H255Q, 1/11:H255Q, 1/11D409H) as opposed to 3 in the controls (n=105) (1/3:N370S, 1/3:H255Q, 1/3:Y108C) (p=0.021, OR 4.2, 95% CI=1.14-15.54). In patients of cohort B 10 carriers of GBA mutations were identified (4/10:L444P, 4/10:D409H;H255Q, 1/10:N370S, 1/10:IVS10-1G→A) as opposed to 4 in controls (n=101) (3/4:N370S, 1/4:L444P). However the difference was not statistically significant (p=0.113, OR 2.5, 95% CI=0.77-8.42). In both cohorts, patients with PD harboring a GBA mutation had an earlier onset of symptoms than non-carriers (p=0.034, p=0.004). The overall difference in the number of carriers identified in PD patients and controls was statistically significant (p=0.006; OR 3.24; 95% CI=1.35-7.81). The association was reinforced in the early onset PD patients (EOPD; n=28, p=0.000, OR 11.37; 95% CI=3.73-34.6). In conclusion GBA mutations were identified with increased frequency in both geographical cohorts of patients with sporadic PD studied compared to control individuals, with the difference being statistically significant only in cohort A. An impressive association with EOPD was found and one third of the EOPD patients examined harbored a GBA mutation. Qualitative differences regarding the type of mutations and/or their relative frequencies were observed between cohorts A and B of PD patients. Genetic and/or environmental factors may account for the observed differences.

Authors+Show Affiliations

Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21745757

Citation

Moraitou, Marina, et al. "Β-Glucocerebrosidase Gene Mutations in Two Cohorts of Greek Patients With Sporadic Parkinson's Disease." Molecular Genetics and Metabolism, vol. 104, no. 1-2, 2011, pp. 149-52.
Moraitou M, Hadjigeorgiou G, Monopolis I, et al. Β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease. Mol Genet Metab. 2011;104(1-2):149-52.
Moraitou, M., Hadjigeorgiou, G., Monopolis, I., Dardiotis, E., Bozi, M., Vassilatis, D., ... Michelakakis, H. (2011). Β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease. Molecular Genetics and Metabolism, 104(1-2), pp. 149-52. doi:10.1016/j.ymgme.2011.06.015.
Moraitou M, et al. Β-Glucocerebrosidase Gene Mutations in Two Cohorts of Greek Patients With Sporadic Parkinson's Disease. Mol Genet Metab. 2011;104(1-2):149-52. PubMed PMID: 21745757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease. AU - Moraitou,Marina, AU - Hadjigeorgiou,Georgios, AU - Monopolis,Ioannis, AU - Dardiotis,Efthimios, AU - Bozi,Maria, AU - Vassilatis,Demitris, AU - Vilageliu,Lluisa, AU - Grinberg,Daniel, AU - Xiromerisiou,Georgia, AU - Stefanis,Leonidas, AU - Michelakakis,Helen, Y1 - 2011/06/24/ PY - 2011/05/16/received PY - 2011/06/17/revised PY - 2011/06/17/accepted PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2012/1/10/medline SP - 149 EP - 52 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 104 IS - 1-2 N2 - An increasing number of clinical, neuropathological and experimental evidence linking Gaucher disease and a spectrum of synucleinopathies, including Parkinson's disease (PD) has emerged over the last decade. In particular, several studies, despite individual differences, have shown that mutations in the β-glucocerebrosidase gene (GBA) are a risk factor for PD. Recently a study from Northern Greece has shown a significant overrepresentation of such mutations only in patients with early onset PD. In the present study 8 different GBA mutations covering 87% of the mutations identified in Gaucher disease patients diagnosed in Greece were investigated in two ethnic Greek cohorts of patients with sporadic Parkinson's disease. Cohort A included patients residing and originating from Thessaly, Central Greece (n=100) and cohort B included patients residing and/or originating from the greater area of Athens (n=105). Age-gender-ethnicity matched healthy individuals from the same areas were included as controls (n=206). In patients of cohort A 11 carriers of GBA mutations were identified (5/11:N370S, 2/11:L444P, 2/11: D409H;H255Q, 1/11:H255Q, 1/11D409H) as opposed to 3 in the controls (n=105) (1/3:N370S, 1/3:H255Q, 1/3:Y108C) (p=0.021, OR 4.2, 95% CI=1.14-15.54). In patients of cohort B 10 carriers of GBA mutations were identified (4/10:L444P, 4/10:D409H;H255Q, 1/10:N370S, 1/10:IVS10-1G→A) as opposed to 4 in controls (n=101) (3/4:N370S, 1/4:L444P). However the difference was not statistically significant (p=0.113, OR 2.5, 95% CI=0.77-8.42). In both cohorts, patients with PD harboring a GBA mutation had an earlier onset of symptoms than non-carriers (p=0.034, p=0.004). The overall difference in the number of carriers identified in PD patients and controls was statistically significant (p=0.006; OR 3.24; 95% CI=1.35-7.81). The association was reinforced in the early onset PD patients (EOPD; n=28, p=0.000, OR 11.37; 95% CI=3.73-34.6). In conclusion GBA mutations were identified with increased frequency in both geographical cohorts of patients with sporadic PD studied compared to control individuals, with the difference being statistically significant only in cohort A. An impressive association with EOPD was found and one third of the EOPD patients examined harbored a GBA mutation. Qualitative differences regarding the type of mutations and/or their relative frequencies were observed between cohorts A and B of PD patients. Genetic and/or environmental factors may account for the observed differences. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/21745757/β_Glucocerebrosidase_gene_mutations_in_two_cohorts_of_Greek_patients_with_sporadic_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(11)00202-2 DB - PRIME DP - Unbound Medicine ER -