Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes

作者：Pascale Esterina^*; Di Battista Maria Elena; Rubino Alfonso; Purcaro Carlo; Valente Marcella; Fattapposta Francesco; Ferraguti Giampiero; Meco Giuseppe

来源：Frontiers in Cellular Neuroscience, 2016, 10: 96.

DOI：10.3389/fncel.2016.00096

• microtubule-associated protein tau gene
• h1 subhaplotype
• Parkinson disease
• non tremor dominant Parkinson disease
• tremor dominant Parkinson disease
• Parkinson subtype

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%; chi(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%; chi(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 Glade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

• 出版日期2016-4-11