Association of the MAPT locus with Parkinson's disease.
OBJECTIVE
Whilst an association between the tau gene (MAPT)-containing H1 haplotype and supranuclear gaze palsy (PSP) has long been recognized, the effect of H1 on risk for Parkinson's disease (PD) has remained more contentious.


METHODS
Herein, we examined the association of H1 and PD in three Caucasian PD patient-control series from Ireland, Norway, and the US (combined: n = 2619), by genotyping two H1/H2 single nucleotide polymorphisms (SNPs) in MAPT (rs1052553) and in the Saitohin gene (rs62063857) and one H1-specific SNP (rs242557).


RESULTS
We identified a significant association between H1/H2 and risk of PD (rs1052553 OR: 1.43, CI: 1.23-1.64; rs62063857 OR: 1.45, CI: 1.27-1.67), but no effect of the H1-specific SNP rs242557 (OR: 0.92, CI: 0.82-1.03).


CONCLUSIONS
Our findings show that the H1 haplotype is a significant risk factor for PD. However, one H1-specific SNP (rs242557) previously implicated in PSP did not alter the risk of PD, indicating that distinct H1 sub-haplotypes probably drive the associations with PD and PSP.
Wider
C
C
Department of Neuroscience, Mayo Clinic, Molecular Genetics Laboratory and Core, Morris K. Udall Parkinsons Disease Research Center of Excellence, Jacksonville, FL 32224, USA. wider.christian@mayo.edu
Vilariño-Güell
C
C
Jasinska-Myga
B
B
Heckman
M G
MG
Soto-Ortolaza
A I
AI
Cobb
S A
SA
Aasly
J O
JO
Gibson
J M
JM
Lynch
T
T
Uitti
R J
RJ
Wszolek
Z K
ZK
Farrer
M J
MJ
Ross
O A
OA
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D008297:Male; D009664:Norway; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013494:Supranuclear Palsy, Progressive / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; C458340:STH protein, human; D016875:tau Proteins