Session Information
Date: Monday, September 23, 2019
Session Title: Genetics
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To assess associations of microtubule associated protein tau (MAPT) H1 subhaplotypes and the H2 haplotype with clinical features in patients with Parkinson`s disease (PD).
Background: The MAPT H1 haplotype has been shown to increase the risk for several neurodegenerative diseases. Little, however, is known about associations of MAPT (sub-)haplotypes with clinical and demographic features in patients with PD.
Method: We included 856 Caucasian patients with PD, who were seen at the Mayo Clinic Florida and who had no known PD-causing mutation. We retrospectively extracted the following clinical and demographic information from patients’ charts: age at PD onset, sex, disease duration, rate of disease progression, survival after PD onset, levodopa use/response, bradykinesia, rigidity, postural instability, resting tremor, postural tremor, dementia, dystonia, dyskinesia, autonomic dysfunction (gastrointestinal, urogenital), impulse control disorder, (pseudo-)hallucinations, depression, orthostatic hypotension, REM sleep behavior disorder (RBD), restless legs syndrome (RLS), and PD subtype (akinetic-rigid, tremor-dominant, gait difficulty, or mixed). Genetic analyses: Five MAPT variants tagging H1 subhaplotypes (rs1467967, rs242557, rs3785883, rs2471738, rs7521) and one H2 haplotype tagging variant (rs8070723) were genotyped (QuantStudio 7 Flex Real-Time PCR system, Applied Biosystems). Genotype call rates were 100% for each variant. Associations were calculated for MAPT H1 subhaplotypes seen in >1% of patients and for the H2 haplotype.
Results: Significant associations (P< 0.0021) were observed between the H1b subhaplotype and a higher risk of orthostatic hypotension (OR=1.72); H1j and a lower risk of resting tremor (OR=0.14) and a higher risk of RBD (OR=3.21); H1r and a lower risk of bradykinesia (OR=0.14); H1v and a higher risk of RLS (OR=5.49). Suggestive associations (P< 0.01) were noted for H1b (dyskinesia), H1f [dystonia, (pseudo-)hallucinations], and H1v (depression). No significant and no suggestive associations of the H2 hapolotype and any clinical or demographic feature studied were observed.
Conclusion: Several MAPT H1 subhaplotypes (H1b, H1j, H1r, and H1v) were significantly associated with specific clinical features seen in PD (orthostatic hypotension, resting tremor, RBD, bradykinesia, and RLS).
To cite this abstract in AMA style:
A. Deutschlander, M. Heckman, T. Konno, M. Ossi, N. Diehl, A. Soto, A. Strongosky, R. Uitti, J. van Gerpen, O. Ross, W. Zbigniew. Associations of microtubule associated protein tau (MAPT) H1 subhaplotypes and the MAPT H2 haplotype with demographic and clinical features in Parkinson`s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/associations-of-microtubule-associated-protein-tau-mapt-h1-subhaplotypes-and-the-mapt-h2-haplotype-with-demographic-and-clinical-features-in-parkinsons-disease/. Accessed September 7, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/associations-of-microtubule-associated-protein-tau-mapt-h1-subhaplotypes-and-the-mapt-h2-haplotype-with-demographic-and-clinical-features-in-parkinsons-disease/