Pooled analysis of iron-related genes in Parkinson's disease: Association with transferrin

Neurobiology of Disease

Jerome I. Rotter¹  Daniel D. Buchanan²  Marie-Anne Loriot³  Jeff M. Bronstein⁴  Kent D. Taylor⁵  Ismaïl Ahmed⁶  Janet S. Sinsheimer⁷  Shannon L. Rhodes⁸  Beate Ritz⁹  Alexis Elbaz^1,10  George D. Mellick^1,11 

[1] Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire, France;Corresponding author.;Princess Alexandra Hospital, Australia;Univ Paris-Sud, UMRS 1018, F-94276 le Kremlin Bicêtre, France;University of Queensland, School of Medicine, Brisbane, Australia;Cancer and Population Studies Group, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane, QLD 4006, Australia;Centre for Research in Epidemiology and Population Health, Biostatistics team, INSERM U1018, F-94276 le Kremlin Bicêtre, France;Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E. Young Drive S, Los Angeles, CA 90095-1772, USA;Department of Human Genetics, David Geffen School of Medicine at UCLA, 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088, USA;Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, 1124 West Carson, Bldg E5, Torrance, CA 90502, USA;Sorbonne Paris Cité, Université Paris Descartes, INSERM UMR-S 775, France;

关键词: Epidemiology;    Genetics;    Pooled-analysis;    Iron homeostasis;    Transferrin;    Transferrin receptor 2;   

DOI  :  

来源: DOAJ

【 摘 要 】

Pathologic features of Parkinson's disease (PD) include death of dopaminergic neurons in the substantia nigra, presence of α-synuclein containing Lewy bodies, and iron accumulation in PD-related brain regions. The observed iron accumulation may be contributing to PD etiology but it also may be a byproduct of cell death or cellular dysfunction. To elucidate the possible role of iron accumulation in PD, we investigated genetic variation in 16 genes related to iron homeostasis in three case–control studies from the United States, Australia, and France. After screening 90 haplotype tagging single nucleotide polymorphisms (SNPs) within the genes of interest in the US study population, we investigated the five most promising gene regions in two additional independent case–control studies. For the pooled data set (1289 cases, 1391 controls) we observed a protective association (OR = 0.83, 95% CI: 0.71–0.96) between PD and a haplotype composed of the A allele at rs1880669 and the T allele at rs1049296 in transferrin (TF; GeneID: 7018). Additionally, we observed a suggestive protective association (OR = 0.87, 95% CI: 0.74-1.02) between PD and a haplotype composed of the G allele at rs10247962 and the A allele at rs4434553 in transferrin receptor 2 (TFR2; GeneID: 7036). We observed no associations in our pooled sample for haplotypes in SLC40A1, CYB561, or HFE. Taken together with previous findings in model systems, our results suggest that TF or a TF-TFR2 complex may have a role in the etiology of PD, possibly through iron misregulation or mitochondrial dysfunction within dopaminergic neurons.

【 授权许可】

Unknown