NURR1 promoter polymorphisms:: Parkinson's disease, schizophrenia, and personality traits

We have previously identified mutations in exon three in NURR1 (NR4A2) in two patients with schizophrenia (SZ) and one patient with bipolar disease with psychotic symptoms. In the present study we analyzed the promoter region of NURR1 and identified five polymorphic sites: three were found to be in strong linkage disequilibrium with a previously identified polymorphic site in the sixth intron. One polymorphism of this haplotype and the two other independent polymorphisms were investigated for their possible association with SZ and Parkinson's disease (PD) by comparing their frequencies in a Swedish material consisting of 134 subjects with SZ and 207 matched controls and 108 subjects with PD and 125 matched controls. Exon 1 was also investigated in our Parkinson and control material but no variances were found. The distributions of the two most informative polymorphisms in the promoter were investigated in an American material as well consisting of 141 subjects with SZ and 139 matched controls. Furthermore, the identified markers were screened for association with putative endophenotypes of SZ in the Swedish material. The distribution of sequence variants among the Swedish controls matched for SZ was investigated with regard to personality. No significant genotype or allelic association of the three sequence variants with SZ or PD was found. Several comparisons regarding endophenotypes or personality indicated association at the 5% confidence level, although correction for multiple testing rendered none of these findings significant. We conclude that the identified polymorphic sites in the human NURR1 are unlikely to be involved in conferring susceptibility for SZ or PD in our patient material. (C) 2003 Wiley-Liss, Inc.