title: Genetic analysis of Nurr1 haplotypes in Parkinson's disease.
abstract: Nurr1 gene plays an important role in the development of the mesencephalic dopaminergic system. Genetic variability of Nurr1 gene may be associated with risk of Parkinson's disease (PD). We found three polymorphic loci (c.-2922(C)2-3, IVS6+18insG and EX8+657 (9-10CA)) of the Nurr1 gene in our PD patients and a novel intron 7+33 C-->T variant in one PD patient. We proceeded to perform a haplotype analysis in a case control study. A total of 202 PD patients (mean age 65.04+/-9.44 years, 55.4% men) and 202 age, gender and race matched controls (mean age 64.33+/-10.12 years, 54.0% men) were studied. The intron 7+33 C-->T variant was present in only one of the PD patients (0.5%) but in none of the controls. The Nurr1 mRNA levels in the lymphocytes did not significantly differ between the affected patient and controls. We found complete linkage disequilibrium between c.-2922(C)2-3 and IVS6+18insG polymorphic loci (D=0.25). Analysis of the three loci haplotype frequencies did not demonstrate any significant difference between PD and controls. There were also no significant differences in the haplotype frequencies between young and late onset PD patients. In conclusion, we demonstrated a large common haplotype block spanning the Nurr1 gene in our population. The intron 7+33 C-->T variant most likely represents either a non-functional mutation or a rare polymorphism in our study population. Our study suggests that Nurr1 variability is unlikely to play a major role in the majority of our PD patients.
authors.affiliation: Division of Research, SingHealth, Singapore, Singapore. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Henry
authors.initials: H
authors.lastname: Chung
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: V R
authors.initials: VR
authors.lastname: Chandran
authors.forename: Chris
authors.initials: C
authors.lastname: Tan
authors.forename: Mei-lin
authors.initials: ML
authors.lastname: Teoh
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yih
authors.forename: Ratnagopal
authors.initials: R
authors.lastname: Pavanni
authors.forename: Meng-Cheong
authors.initials: MC
authors.lastname: Wong
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010300:Parkinson Disease / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors