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- Title
Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system.
- Authors
Severino, Giovanni; Manchia, Mirko; Contu, Paolo; Squassina, Alessio; Lampus, Simona; Ardau, Raffaella; Chillotti, Caterina; Del Zompo, Maria
- Abstract
Objective: The aim of our study was to investigate the association between REV-ERBα gene ( NR1D1) single nucleotide polymorphisms (SNPs) and bipolar disorder (BP) in a case-control sample of Sardinian ancestry and evaluate its effect on age at onset (AAO) of BP. Methods: We genotyped SNPs rs12941497 (SNP1) and rs939347 (SNP2), located, respectively, in the first intron and in the 5′UTR region of the gene, in a sample comprised of 300 bipolar patients and 300 healthy controls of Sardinian ancestry. We also studied AAO by means of admixture analysis, obtaining a cutoff point of age 22 and then carrying out association analysis between the two AAO groups. Results: In the case-control comparison, single marker analysis showed no association for any of the SNPs tested. Haplotype analysis showed a nominally significant association for two haplotypes of SNPs 1-2. Comparing the early- and later-onset groups, nominal association was found for SNP1. Haplotype analysis showed that one haplotype was nominally associated with the later-onset group. Conclusions: Our results, indicating a nominal association of the REV-ERBα gene with BP, suggest a possible role of REV-ERBα in the pathogenesis of BP. Further investigation of larger independent samples and different populations is warranted.
- Subjects
GENETIC polymorphism research; GENETICS of circadian rhythms; BIPOLAR disorder; NUCLEAR receptors (Biochemistry); SARDINIANS
- Publication
Bipolar Disorders, 2009, Vol 11, Issue 2, p215
- ISSN
1398-5647
- Publication type
Article
- DOI
10.1111/j.1399-5618.2009.00667.x