Lack of interaction of SNCA and MAPT genotypes in Parkinson's disease

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