Expression and association analyses of promoter variants of the neurogenic gene HES6, a candidate gene for mood disorder susceptibility and antidepressant response.
Hes6 is a neurogenic gene which is down-regulated in the hippocampi of rats chronically treated with the antidepressant paroxetine. To assess whether variability in HES6 associates with mood disorder diagnosis or antidepressant response, this gene was sequenced in 24 unrelated New Zealand Caucasians. A total of 12 polymorphisms were identified, six of which were in the promoter region of the gene. Haplotypes encompassing the promoter SNPs were studied by cloning the region upstream of the transcription start site, and examining basal transcription rates in luciferase reporter gene assays. SNPs located at positions -1099, -831, -424 and -267 were shown to significantly alter expression of the reporter gene. These four variants were tested for association with mood disorder diagnosis or antidepressant response in a family study of depression, but no significant associations were observed. However, given the importance of this gene in neural function and development, the promoter variants described here may be of wider relevance.
Glubb
Dylan M
DM
Gene Structure & Function Laboratory, Department of Pathology, University of Otago, Christchurch P.O. Box 4345, Christchurch, New Zealand. dylan.glubb@otago.ac.nz
Joyce
Peter R
PR
Kennedy
Martin A
MA
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy / Q000235:genetics*; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D014162:Transfection / Q000379:methods; D044465:White People
D000928:Antidepressive Agents; D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; C411859:HES6 protein, human