Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression.
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Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression. / Schmitt, Ina; Wüllner, Ullrich; Rooyen, van; Pierre, Jan; Khazneh, Hassan; Becker, Julian; Volk, Alexander; Kubisch, Christian; Becker, Tim; Kostic, Vladimir S; Klein, Christine; Ramirez, Alfredo.
In: EUR J HUM GENET, Vol. 20, No. 12, 12, 2012, p. 1265-1269.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression.
AU - Schmitt, Ina
AU - Wüllner, Ullrich
AU - Rooyen, van
AU - Pierre, Jan
AU - Khazneh, Hassan
AU - Becker, Julian
AU - Volk, Alexander
AU - Kubisch, Christian
AU - Becker, Tim
AU - Kostic, Vladimir S
AU - Klein, Christine
AU - Ramirez, Alfredo
PY - 2012
Y1 - 2012
N2 - Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3' untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3' region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3'UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.
AB - Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3' untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3' region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3'UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Alleles
KW - Case-Control Studies
KW - MicroRNAs/metabolism
KW - Transcription, Genetic
KW - Polymorphism, Single Nucleotide
KW - 3' Untranslated Regions
KW - Parkinson Disease/genetics
KW - alpha-Synuclein/genetics/metabolism
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Alleles
KW - Case-Control Studies
KW - MicroRNAs/metabolism
KW - Transcription, Genetic
KW - Polymorphism, Single Nucleotide
KW - 3' Untranslated Regions
KW - Parkinson Disease/genetics
KW - alpha-Synuclein/genetics/metabolism
M3 - SCORING: Journal article
VL - 20
SP - 1265
EP - 1269
JO - EUR J HUM GENET
JF - EUR J HUM GENET
SN - 1018-4813
IS - 12
M1 - 12
ER -
