Stargazin involvement with bipolar disorder and response to lithium treatment
| Autor: | Leonardo Tondo, Gianfranco Floris, David St Clair, Robert Kerwin, Gilad Silberberg, David A. Collier, Janet Munro, Gerome Breen, Ruth Navon, Anat Levit |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Oncology Psychosis medicine.medical_specialty Bipolar Disorder Genotype Lithium (medication) Drug Resistance Gene Expression Single-nucleotide polymorphism Polymorphism Single Nucleotide behavioral disciplines and activities Linkage Disequilibrium Cohort Studies Internal medicine mental disorders Genetics medicine Humans RNA Messenger Bipolar disorder General Pharmacology Toxicology and Pharmaceutics Molecular Biology Genetics (clinical) Aged Genetic association Aged 80 and over CACNG2 biology business.industry Middle Aged medicine.disease Antidepressive Agents Schizophrenia Case-Control Studies Chromosomal region Lithium Compounds biology.protein Molecular Medicine Female Calcium Channels business medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 18:403-412 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0b013e3282f974ca |
| Popis: | OBJECTIVES Multiple reports have implicated chromosomal region 22q13.1 in both schizophrenia and bipolar disorder. The calcium channel gamma-2 subunit gene (cacng2, Stargazin) located on 22q13.1 was recently reported to be associated with schizophrenia. We aimed to examine the expression levels of Stargazin in post-mortem brain samples of patients with schizophrenia, patients with bipolar disorder (BPD) and healthy controls, test for genetic association between Stargazin and these disorders and test for genetic association between Stargazin and response to lithium treatment. METHODS Expression analysis was carried out by quantitative reverse transcription-PCR in RNA samples from dorsolateral prefrontal cortices of patients with schizophrenia, patients with BPD and controls (n=35 each). Twelve single nucleotide polymorphisms encompassing Stargazin were genotyped in DNA samples from two cohorts, 'Aberdeen' and 'Cagliari' (n=410, 170, respectively). Patients were treated with lithium and divided into groups according to their response. RESULTS A 1.6-fold overexpression of Stargazin was observed in patients with BPD (P=0.000036). No difference in expression was observed in patients with schizophrenia. None of the 12 genotyped single nucleotide polymorphisms were associated with BPD, but three of them were significantly associated with lithium response: one in both cohorts (rs2284017) and two (rs2284018, rs5750285) each in a different cohort. Haplotype analysis revealed significant 'response-protective' and 'response-inhibitive' haplotypes in both cohorts. CONCLUSION Our findings suggest that Stargazin dysregulation may be involved with the pathophysiology of BPD, but not with that of schizophrenia, and that Stargazin polymorphisms may play a role in the response to lithium treatment. |
| Databáze: | OpenAIRE |
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