Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: To search for abnormal NRE in the following genes: ATXN2, ATXN3, CACNA1A, TBP, c9orf72, PRNP, POLG1A and TOMM40 in a Swedish PD cohort.
Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder after Alzheimer’s disease. Genetic alterations have been proposed as key risk factors associated with PD. Nucleotide Repeat Expansions (NRE) of variable range in ATXN2, ATXN3, CACNA1A, TBP, c9orf72, PRNP, POLG1A and TOMM40 have been described as significant risk factors for PD and other neurodegenerative diseases. However, these genes have not been analyzed in Swedish PD patients.
Methods: We analyzed DNA samples from 215 Swedish PD patients and 546 ethnically matched controls.
Results: ATXN2: Intermediate CAG repeats expansions in ATXN2 were significantly associated with PD (12/426, 2.77% vs 10/1093 0.91%, p≤0.0003). The specific cut-off for large repeats was 27 CAG repeats. In addition, we found novel structural variations in the ATXN2. Interestingly, CAG repeats ≥42-48 units in TBP were also found in our cohort, (3/426, 0.69% vs 1/1093 0.091, p≤0.04). Also significant association was found between non-10/non-11 alleles in POLG1 and PD (43/422, 10% vs 65/1070, 6%, p≤0.005). TOMM40/ApoE: ApoE alleles were not preferentially associated with PD, the genotype Long-Very/long poly-T sequence in TOMM40 showed to be more frequent in PD 12.20% than in controls 5.98% (p≤0.05). Intermediate or pathological c9orf72 HEX: G4C2 hexa-nucleotides repeats in c9orf72 were also associated with PD (8/213 (1.87%) p≤0.00). Neither pathological poly-Q tails nor insertional nucleotides were present in ATXN3, CACNA1A and PRNP associated with PD.
Conclusions: These data confirmed NRE with abnormal repeats in ATXN2, TBP, POLG1, TOMM40 and c9orf72 as genetic risk factors for PD in the Swedish population. Our results do not support the role of pathological (or conferring risk) expansions or other polymorphisms in ATXN3, CACNA1A and PRNP as genetic risk factors for PD in Sweden.
To cite this abstract in AMA style:J. Laffita Mesa, L. Brodin, P. Svenningsson. Nucleotide repeats as genetic risk factors in a Swedish Parkinson’s disease cohort [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/nucleotide-repeats-as-genetic-risk-factors-in-a-swedish-parkinsons-disease-cohort/. Accessed November 29, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/nucleotide-repeats-as-genetic-risk-factors-in-a-swedish-parkinsons-disease-cohort/