Stargazin involvement with bipolar disorder and response to lithium treatment.
OBJECTIVE
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.


CONCLUSIONS
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.
Silberberg
Gilad
G
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Levit
Anat
A
Collier
David
D
St Clair
David
D
Munro
Janet
J
Kerwin
Robert W
RW
Tondo
Leonardo
L
Floris
Gianfranco
G
Breen
Gerome
G
Navon
Ruth
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics
D000928:Antidepressive Agents; C491912:CACNG2 protein, human; D015220:Calcium Channels; D018020:Lithium Compounds; D012333:RNA, Messenger