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).

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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/