European Neurology
Original Paper
Serotonin Transporter Gene Polymorphic Element 5-HTTLPR Increases the Risk of Sporadic Parkinson’s Disease in ItalyAlbani D.a · Vittori A.a · Batelli S.a · Polito L.a · De Mauro S.a · Galimberti D.b · Scarpini E.b · Lovati C.c · Mariani C.c · Forloni G.aaDepartment of Neuroscience, Mario Negri Institute for Pharmacological Research, bDepartment of Neurological Sciences, Dino Ferrari Centre, University of Milan, Ospedale Maggiore Policlinico, and cNeurology Unit, University of Milan, Luigi Sacco Hospital, Milan, Italy
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Article / Publication Details
Received: January 09, 2009
Accepted: April 21, 2009
Published online: June 12, 2009
Issue release date: July 2009
Number of Print Pages: 4
Number of Figures: 0
Number of Tables: 2
ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)
For additional information: https://www.karger.com/ENE
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder causing muscular rigidity, resting tremor and bradykinesia. We conducted an association study assessing how PD risk in Italy was influenced by the serotonin transporter gene (SLC6A4) polymorphic region 5-HTTLPR, consisting of an insertion/deletion (long allele-L/short allele-S) of 43 bp in the SLC6A4 promoter region. The SLC6A4 promoter single nucleotide polymorphism rs25531(A→G) was evaluated too. We collected 837 independent subjects (393 PD, 444 controls). An association between the 5-HTTLPR polymorphism and risk of PD (S/S genotype OR [95% CI]: 1.7[1.2–2.5], p = 0.002) was found. The rs25531 and the haplotype 5-HTTLPR/rs25531 did not associate with risk of PD. Our data indicate that the 5-HTTLPR polymorphic element within the SLC6A4 promoter may govern the genetic risk of PD in Italians.
© 2009 S. Karger AG, Basel
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References
-
Von Campenhausen S, Bornschein B, Wick R, Bötzel K, Sampaio C, Poewe W, Oertel W, Siebert U, Berger K, Dodel R: Prevalence and incidence of Parkinson’s disease in Europe. Eur Neuropsychopharmacol 2005;4:473–490.
External Resources
- Belin AC, Westerlund M: Parkinson’s disease: a genetic perspective. FEBS J 2008;275:1377–1383.
- Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A: Genetics of Parkinson’s disease and parkinsonism. Ann Neurol 2006;60:389–398.
-
The Michael J. Fox Foundation and the Alzheimer Research Forum: A database for Parkinson’s disease genetic association studies developed by Massachusetts General Hospital/Harvard Medical School (www.pdgene.org).
- Bonifati V: LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson’s disease. Neurochem Res 2007;32:1700–1708.
- Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI, Mata IF, Lee-Chen GJ, Chen CM, Tang M, Zhao Y, Hattori N, Farrer MJ, Tan EK, Wu RM: Analysis of Lrrk2 R1628P as a risk factor for Parkinson’s disease. Ann Neurol 2008;64:88–92.
- Kish SJ, Tong J, Hornykiewicz O, Rajput A, Chang LJ, Guttman M, Furukawa Y: Preferential loss of serotonin markers in caudate versus putamen in Parkinson’s disease. Brain 2008;131:120–131.
- Guttman M, Boileau I, Warsh J, Saint-Cyr JA, Ginovart N, McCluskey T, Houle S, Wilson A, Mundo E, Rusjan P, Meyer J, Kish SJ: Brain serotonin transporter binding in non-depressed patients with Parkinson’s disease. Eur J Neurol 2007;14:523–528.
- Zhang X, Andren PE, Greengard P, Svenningsson P: Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of parkinsonism. Proc Natl Acad Sci USA 2008;105:2163–2168.
- Kish SJ: Biochemistry of Parkinson’s disease: is a brain serotonergic deficiency a characteristic of idiopathic Parkinson’s disease? Adv Neurol 2003;91:39–49.
- Kiferle L, Ceravolo R, Petrozzi L, Rossi C, Frosini D, Rocchi A, Siciliano G, Bonuccelli U, Murri L: Visual hallucinations in Parkinson’s disease are not influenced by polymorphisms of serotonin 5-HT2A receptor and transporter genes. Neurosci Lett 2007;422:228–231.
- Murphy DL, Lerner A, Rudnick G, Lesch KP: Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 2004;4:109–123.
- Maeda T, Nagata K, Yoshida Y, Kannari K: Serotonergic hyperinnervation into the dopaminergic denervated striatum compensates for dopamine conversion from exogenously administered L-DOPA. Brain Res 2005;1046:230–233.
- Kannari K, Shen H, Arai A, Tomiyama M, Baba M: Reuptake of L-DOPA-derived extracellular dopamine in the striatum with dopaminergic denervation via serotonin transporters. Neurosci Lett 2006;402:62–65.
- Nakamura M, Ueno S, Sano A, Tanabe H: The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 2000;5:32–38.
- Kraft JB, Slager SL, McGrath PJ, Hamilton SP: Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry 2005;58:374–381.
- Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL: Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 2006;11:224–226.
- Dannlowski U, Ohrmann P, Bauer J, Kugel H, Baune BT, Hohoff C, Kersting A, Arolt V, Heindel W, Deckert J, Suslow T: Serotonergic genes modulate amygdala activity in major depression. Genes Brain Behav 2007;6:672–676.
-
Hastings WK: Monte Carlo sampling methods using Markov chains and their applications. Biometrika 1970;57:97–109.
External Resources
-
Miller MP: R by C: a program that performs Fisher’s exact test on any sized contingency table through the use of the Metropolis algorithm (www.marksgeneticsoftware.net).
-
Preacher KJ: Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence [computer software] (www.quantpsy.org), 2001.
Article / Publication Details
Received: January 09, 2009
Accepted: April 21, 2009
Published online: June 12, 2009
Issue release date: July 2009
Number of Print Pages: 4
Number of Figures: 0
Number of Tables: 2
ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)
For additional information: https://www.karger.com/ENE
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