Evaluation of FGF 20 variants for susceptibility to Parkinson's disease in Eastern Indians. (14th May 2018) - Sadhukhan, Dipanwita
Highlights: The role of FGF20 was evaluated in Eastern Indian PD patients using two 3′-UTR SNPs. Between rs1721100 and rs12720208 the former was observed to be associated with PD. However, a specific haplotype of these two SNPs confers protection from the disease. Regulatory role of rs1721100 on FGF20 expression was elucidated by functional study. Our data support recent report on meta analysis on association of these SNPs with PD. 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 mi R -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.