MAPT H1 haplotype is a risk factor for essential tremor and multiple system atrophy

Mutations in the microtubule-associated protein tau gene ( MAPT ) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).1 In addition, the major common MAPT- containing H1 haplotype is associated with increased risk for 2 parkinsonian disorders: progressive supranuclear palsy (PSP) characterized by 4-repeat tau pathology and Parkinson disease (PD) with α-synuclein pathology.2,3 However, the role of MAPT variation in other disorders with similar pathology or disease phenotype is unclear. We investigated the frequency of the MAPT H1 haplotype in both essential tremor (ET) and multiple system atrophy (MSA). ET is the most common movement disorder, and prior evidence has indicated a common link between ET and PD from clinical, epidemiologic, and pathologic studies as well as some reports of brainstem Lewy bodies at autopsy in patients with ET.4 MSA is a neurodegenerative disorder with α-synuclein pathology with a mixed clinical presentation combining autonomic dysfunction, parkinsonism, and cerebellar or pyramidal symptoms. The initial clinical signs of MSA with prominent parkinsonism can make it difficult to differentially diagnose it from early PD. In addition, up to 30% of patients with MSA with prominent parkinsonism may have a transient response to levodopa therapy.5 ### Methods. Genotyping of the MAPT H1 discriminating SNP (rs1052553) and H1c subhaplotype SNP (rs242557) was performed on a Sequenom MassArray iPLEX platform (San Diego, CA) (primer sequences are available on request) and analyzed with Typer 4.0 software. The rate of genotype calls was ≥95% in each population. The series contained 356 patients with clinical ET, 61 patients with pathologically confirmed MSA, and 409 US control subjects; all samples are North American Caucasians. Numerical variables were summarized with the sample mean, SD, and range (table e-1 on the …