Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease

Joelle M. Van Der Walt, Maher A. Noureddine, Raja Kittappa, Michael A. Hauser, William K. Scott, Ron McKay, Fengyu Zhang, Jeffrey M. Stajich, Kenichiro Fujiwara, Burton L. Scott, Margaret A. Pericak-Vance, Jeffery M. Vance, Eden R. Martin

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115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1121-1127
Number of pages7
JournalAmerican journal of human genetics
Volume74
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Van Der Walt, J. M., Noureddine, M. A., Kittappa, R., Hauser, M. A., Scott, W. K., McKay, R., Zhang, F., Stajich, J. M., Fujiwara, K., Scott, B. L., Pericak-Vance, M. A., Vance, J. M., & Martin, E. R. (2004). Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. American journal of human genetics, 74(6), 1121-1127. https://doi.org/10.1086/421052