The PDLIM5 gene and lithium prophylaxis: an association and gene expression analysis in Sardinian patients with bipolar disorder.
A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. In order to evaluate whether PDLIM5 expression interacts with lithium response, we carried out gene expression analysis in lymphoblastoid cells of 30 bipolar patients. No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score<or=6). Our negative findings do not exclude involvement of PDLIM5 in lithium prophylaxis, and further investigation is warranted.
Squassina
Alessio
A
Section of Clinical Pharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, SS 554, km. 4,500, 09042 Monserrato, Cagliari, Italy. cortgen@yahoo.it
Congiu
Donatella
D
Manconi
Francesca
F
Manchia
Mirko
M
Chillotti
Caterina
C
Lampus
Simona
S
Severino
Giovanni
G
Zompo
Maria Del
MD
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007558:Italy; D060588:LIM Domain Proteins; D018020:Lithium Compounds / Q000627:therapeutic use*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D018020:Lithium Compounds; C512485:PDLIM5 protein, human; D051744:Protein Kinase C-epsilon