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LETTER TO THE EDITOR
Lack of interaction of SNCA and
MAPT genotypes in Parkinson’s
disease
T. Botta-Orfilaa,b, M. Ezquerraa,c,
J. Rıosd, R. Fernandez-Santiagoa,
S. Cervantesc,e,f, L. Samaranchc,e,
P. Pastorc,e,f, M. J. Martıa,c, E. Munoza,c,
F. Valldeoriolaa,c, M. Aguilarg,
M. Calopah, J. Hernandez-Varai and
E. Tolosaa,b,c
aParkinson�s Disease-Movement Disorders
Unit-Neurology Service, Hospital Clınic-
IDIBAPS-Universitat de Barcelona,
Barcelona; bNeurological Tissue Bank,
Universitat de Barcelona-Hospital Clınic,
Barcelona; cCenter for Networker Bio-
medical Research in Neurodegenerative
Diseases (CIBERNED); dUniversitat
Autonoma de Barcelona-Statistics and
MethodologySupportUnit,Hospital Clınic-
IDIBAPS, Barcelona; eNeurogenetics Lab-
oratory-Division of Neurosciences, CIMA,
Pamplona; fDepartment of Neurology,
School of Medicine-Clınica Universitaria de
Navarra, Pamplona; gHospital Mutua de
Terrassa-Neurology Service, Terrassa;hHospital de Bellvitge-Neurology Service,
l’Hospitalet de Llobregat, Barcelona; andiHospital Vall d’Hebron-Neurology Service,
Barcelona, Spain
Received 4 August 2010
Accepted 14 September 2010
Correspondence: Dr Mario Ezquerra,
Neurology Service-Hospital Clınic,
Villarroel 170, 08036 Barcelona, Spain
(tel.: +34 932275400 ext 2908; fax:
+34 932275783; e-mail: ezquerra@
clinic.ub.es).
Keywords: genetic association study,
movement disorders, MAPT, SNCA,
Parkinson�s disease
It has been described that a-synuclein(SNCA) and tau (MAPT) polymorphisms
are associated with increased risk for
Parkinson�s disease (PD) [1,2]. Further-
more, a recent study reported the presence
of an interaction risk effect between the
rs356219 in SNCA and H1 haplotype in
MAPT [3]. In contrast, another study
reported no genetic interaction between
the PD-associated Rep1 polymorphism, in
the promoter of SNCA, and the MAPT
H1/H1 genotype [4].
We tested the possible synergistic risk
effect by genotyping the pre-designed
TaqMan assays rs356219 (SNCA) and
rs1800547 (MAPT-H1/H2) on a
StepOnePlus Real-time PCR System
(Applied Biosystems, Foster City, CA,
USA), in 757 unrelated clinically defined
patients with PD and 708 controls
(56.80% and 42.37% were men, respec-
tively; mean age was 68.35 ± 10.46 and
69.42 ± 13.42, respectively). All the indi-
viduals were Caucasians from Spain.
Research protocols were performed after
written informed consent of the subjects
and approval by the Ethics Committees of
the respective centers. Allele frequencies
for both SNPs were in Hardy–Weinberg
equilibrium. Gender did not influence
significantly the associations and thus was
not entered finally into the model.
Single locus analysis showed that G/G
SNCA and H1/H1 MAPT risk genotypes
were over-represented in patients with PD
compared with controls (Table 1).
Logistic regression analysis showed
that both risk genotypes are significantly
associated with PD (Odds Ratio = 1.89
and 1.54, respectively; P £ 0.00005). Nev-
ertheless, no significant multiplicative
interaction between the two genes was
found (P = 0.33, Table 1).
With the limited number of samples
analyzed, our study does not support that
genetic variability in the SNCA and
MAPT genes shows multiplicative inter-
action, but an additive risk effect.
Acknowledgements
This project was supported by grants from
Fondo de Investigaciones Sanitarias to
Dr. Mario Ezquerra (U-2004-FS041184-
O). We acknowledge support provided by
Ana Camara (nurse) and Manel
Fernandez (technician).
References
1. Maraganore DM, de Andrade M, Elbaz A,
et al. Collaborative analysis of alpha-
synuclein gene promoter variability and
parkinson disease. J Am Med Assoc 2006;
296: 661–670.
2. Pastor P, Ezquerra M, Munoz E, et al.
Significant association between the tau gene
A0/A0 genotype and parkinson�s disease.Ann Neurol 2000; 47: 242–245.
3. Goris A, Williams-Gray CH, Clark GR,
et al. Tau and alpha-synuclein in
susceptibility to, and dementia in,
Parkinson�s disease. Ann Neurol 2007;
62: 145–153.
4. Mamah CE, Lesnick TG, Lincoln SJ, et al.
Interaction of alpha-synuclein and tau
genotypes in Parkinson�s disease. AnnNeurol 2005; 57: 439–443.
Table 1 Genotypic and interaction analysis for SNCA and MAPT in PD risk
PD
cases (%)
Controls
(%)
OR
(95% CI) P-value
Genotype
SNCA rs356219
G/G 132 (17.44) 71 (10.03) 1.89 (1.39–2.58) 5.00 E-05
A/G 355 (46.90) 323 (45.62) Reference
A/A 270 (35.67) 314 (44.35) Reference
MAPT rs1800547
H1/H1 452 (59.71) 347 (49.01) 1.54 (1.25–1.90) 4.11 E-05
H1/H2 261 (34.48) 293 (41.38) Reference
H2/H2 44 (5.81) 68 (9.60) Reference
N total 757 708
MAPT–SNCA interaction
MAPT
H1/H1
SNCA
G/G
+ + 84 (11.10) 33 (4.66) 3.20 (2.07–4.94) 5.30 E-08
+ ) 368 (48.61) 314 (44.35) 1.47 (1.18–1.84) 6.35 E-04
) + 48 (6.34) 38 (5.37) 1.59 (1.01–2.50) 4.58 E-02
) ) 257 (33.95) 323 (46.33) Reference
N total 757 708
SNCA
(adjusted for MAPT)
1.88 (1.38–2.56) 1.37E-04
MAPT
(adjusted for SNCA)
1.53 (1.25–1.89) 1.15E-04
Interaction term 3.27E-01
OR, Odds ratio; CI, confidence interval; +, risk genotype; ), rest of genotypes; MAPT,
microtubule-associated protein MAPT gene; SNCA, a-synuclein gene; PD, Parkinson�s disease.
e32� 2010 The Author(s)
European Journal of Neurology � 2010 EFNS
European Journal of Neurology 2011, 18: e32 doi:10.1111/j.1468-1331.2010.03245.x