a4e46286-78f2-40dd-b1d2-4fad449ca942
title
Fibroblast growth factor 20  polymorphisms and haplotypes strongly influence risk of Parkinson disease.
374534de-fc5c-4de1-a98e-8f546fc66bab
abstract
The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor ( FGF20 ) in the survival of dopaminergic cells.  FGF20  is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether  FGF20  influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the  FGF20  gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP,  rs1989754  (P=.0006), and two SNPs,  rs1721100  (P=.02) and  ss20399075  (P=.0008), located in the 3' regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (P=.0003), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (P=.0009). Our results strongly support  FGF20  as a risk factor for PD.