Association of MAPT subhaplotypes with clinical and demographic features in Parkinson’s disease

Abstract

Objective To determine whether distinct microtubule‐associated protein tau MAPT H1 subhaplotypes are associated with clinical and demographic features in Parkinson’s disease. Methods A retrospective cohort study included 855 unrelated Caucasian patients with Parkinson’s disease who were seen by Movement Disorder specialists at the Mayo Clinic Florida between 1998 and 2016. The primary outcome measures were specific demographic and clinical features of Parkinson’s disease, including age at onset, disease progression, survival, motor signs, dementia, dystonia, dyskinesia, autonomic dysfunction, impulse control disorder, psychiatric features, REM sleep behavior disorder, restless legs syndrome, and Parkinson’s disease subtype. Specific clinical features were measured at the initial visit and most recent visit. These outcomes were assessed for association with MAPT H1 subhaplotypes, which were defined by six haplotype tagging variants. Results Median onset age was 64 years (range: 22‐94 years); 548 (64%) of patients were male. Significant associations (P < 0.0029) were observed between MAPT H1b and orthostatic hypotension (OR = 1.72, P = 0.001); between H1j and rest tremor (OR = 0.15; P < 0.001) as well as REM sleep behavior disorder (OR = 3.87, P < 0.001); between H1r and bradykinesia (OR = 0.11; P < 0.001); and between H1v and restless legs syndrome (OR = 4.02, P = 0.002). Interpretation Four MAPT H1 subhaplotypes, but not the H2 haplotype, were significantly associated with specific clinical features in Parkinson’s disease. MAPT haplotypic structure may explain some of the phenotypic variability in disease. Replication of our findings will be critical to fully resolve the Parkinson’s disease risk association signal at Chr17q21.

Transcript Variants of Genes Involved in Neurodegeneration Are Differentially Regulated by the APOE and MAPT Haplotypes

“…Microtubule-associated protein tau (MAPT) is considered a significant risk factor for neurodegenerative diseases, including PD [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Tau protein is biochemically well-characterised and its role in aggregation and neurodegeneration was well established [ 18 ].…”

Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson’s Disease Patients

“…These disorders alter the level of neuroactive substances and metabolites produced by the intestinal flora to a certain extent. Furthermore, the International Parkinson and Movement Disorder Society [ 13 ] positions the positive likelihood ratio of constipation to the diagnosis of prodromal PD at 2.2. Regarding this correlation, regulating the intestinal flora of PD patients has become a current research direction.…”

Genetic architecture of Parkinson’s disease subtypes – Review of the literature

“…Pathogenic variants in MAPT , encoding microtube-associated protein tau, were described in various forms of inherited neurodegenerative disorders ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ). Most of them manifested with autosomal dominant atypical parkinsonisms and dementia; however, in rare cases, they presented as classic PD ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ). Recently, the MAPT locus was divided into two main haplotypes, H1 and H2 ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ).…”

“…Most of them manifested with autosomal dominant atypical parkinsonisms and dementia; however, in rare cases, they presented as classic PD ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ). Recently, the MAPT locus was divided into two main haplotypes, H1 and H2 ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ). The H1 haplotype is the most common, occurring in more than 80% of the general population, and associated with an increased risk of PD, atypical parkinsonisms, Alzheimer’s disease, and multiple other neurodegenerative diseases ( Paul et al, 2016 ; Deutschlander et al, 2020 ; Dulski et al, forthcoming ).…”