Dipanwita Sadhukhan1, Gautami Das1, Arindam Biswas1, Soumitra Ghosh1, Shyamal K Das2, Kunal Ray3, Jharna Ray4. 1. S.N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India. 2. Movement Disorders Clinic, Bangur Institute of Neurosciences, Kolkata, India. 3. Academy of Scientific & Innovative Research, New Delhi, India. 4. S.N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India. Electronic address: jharnaray@gmail.com.
Abstract
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease and has a complex etiology. Single nucleotide polymorphisms in the 3'-untranslated region of Fibroblast growth factor 20 (FGF 20) have been reported to be associated with PD; however, the results are controversial. Although FGF20 enhances the survival of dopaminergic neurons, it may also result in PD susceptibility by altering alpha-synuclein expression. MATERIALS AND METHODS: To identify and characterize genetic risk variants in FGF 20 in Eastern Indian PD patients, 2 SNPs of FGF 20 (rs1721100 and rs2720208) were genotyped in 336 PD cases and 313 ethnically matched controls by PCR-RFLP. RESULTS: We observed statistically significant differences in genotypic and allelic frequencies of rs1721100 between PD cases and controls but not for rs12720208. Haplotype G-C showed a significant protective effect against PD. A functional assay revealed that the risk allele C at rs1721100 has little or no effect on relative luciferase activity from a reporter construct in the presence of miR-3189-3p, whereas allele G results in significant dose-dependent reduction. CONCLUSION: Our results suggest that FGF 20 is a susceptibility gene for PD in Eastern Indians.
BACKGROUND:Parkinson's disease (PD) is the second most common neurodegenerative disease and has a complex etiology. Single nucleotide polymorphisms in the 3'-untranslated region of Fibroblast growth factor 20 (FGF 20) have been reported to be associated with PD; however, the results are controversial. Although FGF20 enhances the survival of dopaminergic neurons, it may also result in PD susceptibility by altering alpha-synuclein expression. MATERIALS AND METHODS: To identify and characterize genetic risk variants in FGF 20 in Eastern Indian PDpatients, 2 SNPs of FGF 20 (rs1721100 and rs2720208) were genotyped in 336 PD cases and 313 ethnically matched controls by PCR-RFLP. RESULTS: We observed statistically significant differences in genotypic and allelic frequencies of rs1721100 between PD cases and controls but not for rs12720208. Haplotype G-C showed a significant protective effect against PD. A functional assay revealed that the risk allele C at rs1721100 has little or no effect on relative luciferase activity from a reporter construct in the presence of miR-3189-3p, whereas allele G results in significant dose-dependent reduction. CONCLUSION: Our results suggest that FGF 20 is a susceptibility gene for PD in Eastern Indians.
Authors: Zaipul I Md Dom; Eiichiro Satake; Jan Skupien; Bozena Krolewski; Kristina O'Neil; Jill A Willency; Simon T Dillon; Jonathan M Wilson; Hiroki Kobayashi; Katsuhito Ihara; Towia A Libermann; Marlon Pragnell; Kevin L Duffin; Andrzej S Krolewski Journal: Sci Transl Med Date: 2021-06-30 Impact factor: 19.319