BACKGROUND: Microtubule-associated protein tau (
MAPT) has been associated with several
neurodegenerative disorders including forms of
parkinsonism and
Parkinson disease (PD). We evaluated the association of the
MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition,
postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat
isoforms of
MAPT, and neighboring genes Saitohin (
STH) and
KIAA1267, are altered in PD
cerebellum. METHODS: Twenty-one
single-nucleotide polymorphisms (
SNPs) in the region of
MAPT on
chromosome 17q21 were genotyped in the GenePD Study. Single
SNPs and
haplotypes, including the H1
haplotype, were evaluated for association to PD. Relative quantification of
gene expression was performed using real-time
RT-PCR. RESULTS: After adjusting for
multiple comparisons,
SNP rs1800547 was significantly associated with PD affection. While the H1
haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat
MAPT,
STH, and
KIAA1267 was significantly increased in PD
brains relative to controls. No difference in expression was observed for 3-repeat
MAPT. CONCLUSIONS: This study supports a role for
MAPT in the
pathogenesis of familial and
idiopathic Parkinson disease (PD). Interestingly, the results of the
gene expression studies suggest that other genes in the vicinity of
MAPT, specifically
STH and
KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.
