title: Polymorphisms in iron-responsive binding protein 2 and lack of association with sporadic Parkinson's disease.
abstract: Mice with targeted disruptions in the iron-responsive binding protein 2 (IRP2) gene accumulate iron in distinct regions of the brain and develop neurodegenerative characteristics resembling Parkinson's disease after 6 months of age. To determine whether polymorphisms in IRP2 predispose humans to Parkinson's disease (PD), we sequenced the IRP2 gene of subjects with sporadic PD and normal controls. Three polymorphisms which result in an amino acid change were identified: L159V, F272L, and T560I. The L159V and T560I polymorphisms, identified in an African-American PD subject, were found in the African-American population at an allele frequency of 0.102 (n = 1,236) and 0.111 (n = 1,228), respectively, and were not associated with an increased prevalence of PD. The F272L polymorphism was found in a normal 58-year-old, Caucasian subject whose father had PD, but it was not observed in 38 additional patients with sporadic PD. The F272L polymorphism occurred at an allele frequency of 0.0014 (n = 1,384) in the normal Caucasian population. Additional F272L heterozygous subjects identified in the normal population did not have a family or personal history of PD. We conclude that these IRP2 polymorphisms do not play an important role in the development of sporadic cases of PD. It remains to be determined whether other polymorphisms in IRP2 play a role in familial PD.
authors.affiliation: The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, California 92037, USA. plee@scripps.edu
authors.forename: Pauline L
authors.initials: PL
authors.lastname: Lee
authors.forename: Terri
authors.initials: T
authors.lastname: Gelbart
authors.forename: Carol
authors.initials: C
authors.lastname: West
authors.forename: Carol
authors.initials: C
authors.lastname: Halloran
authors.forename: Jack C
authors.initials: JC
authors.lastname: Sipe
authors.forename: Ernest
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000368:Aged; D000483:Alleles; D044383:Black People / Q000235:genetics; D002884:Chromosomes, Human, Pair 15; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005828:Genetics, Population; D006801:Humans; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D035942:Iron Regulatory Protein 2