title: Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.
abstract: The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ(2) = 9.9; OR, 1.7; 95% CI, 1.2-2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ(2) = 13.6; OR, 2.03; 95% CI, 1.4-3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3-6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University Rome, Italy.
authors.forename: Esterina
authors.initials: E
authors.lastname: Pascale
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza UniversityRome, Italy; Research Centre of Social Diseases (CIMS), Sapienza UniversityRome, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Di Battista
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza UniversityRome, Italy; Research Centre of Social Diseases (CIMS), Sapienza UniversityRome, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rubino
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza UniversityRome, Italy; Research Centre of Social Diseases (CIMS), Sapienza UniversityRome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Purcaro
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza UniversityRome, Italy; Research Centre of Social Diseases (CIMS), Sapienza UniversityRome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Valente
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza University Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fattapposta
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University Rome, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Ferraguti
authors.affiliation: Department of Neurology and Psychiatry (Parkinson's Centre), Sapienza UniversityRome, Italy; Research Centre of Social Diseases (CIMS), Sapienza UniversityRome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Meco
keywords: Parkinson disease; Parkinson subtype; h1 subhaplotype; microtubule-associated protein tau gene; non tremor dominant Parkinson disease; tremor dominant Parkinson disease