title: Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.
abstract: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of PD. When the GG genotypes of the IL-6 and ERbeta SNPs were combined, the combination was much more robustly associated with PD, and especially with PD with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing PD, particularly regarding early age of onset PD, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene.
authors.affiliation: Department of Pharmacology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. anna.hakansson@pharm.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Håkansson
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Silvia
authors.initials: S
authors.lastname: Buervenich
authors.forename: Andrea
authors.initials: A
authors.lastname: Carmine
authors.forename: Björn
authors.initials: B
authors.lastname: Holmberg
authors.forename: Olof
authors.initials: O
authors.lastname: Sydow
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Bo
authors.initials: B
authors.lastname: Johnels
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
mesh_terms: D017668:Age of Onset; D000483:Alleles; D047629:Estrogen Receptor beta / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015810:Linkage Disequilibrium; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D047629:Estrogen Receptor beta; D015850:Interleukin-6