A splice site polymorphism in the G-protein beta subunit influences antidepressant efficacy in depression

作者：Wilkie Murray J V; Smith Daniel; Reid Ian C; Day Richard K; Matthews Keith; Wolf Charles Roland; Blackwood Douglas; Smith Gillian^*

来源：Pharmacogenetics and Genomics, 2007, 17(3): 207-215.

DOI：10.1097/FPC.0b013e32801a3be6

• antidepressant response
• brain-derived neurotrophic factor
• CREB
• G-protein
• pharmacogenetics

Objective Recent evidence suggests that signalling cascades located downstream of monoamine receptors are altered following antidepressant treatment. Our objective was to investigate whether genetic polymorphisms in genes involved in these signalling cascades influenced antidepressant efficacy.
Methods Polymorphisms in the G-protein beta subunit GNB3, the cAMP response element binding protein 1 gene (CREB1), the brain derived neurotrophic factor (BDNF) and CREB binding protein (CREBBP) were studied in well characterised unipolar (n = 166) and early onset (n = 102) depressive populations and correlated with treatment response.
Results The GNB3 C825T polymorphism, which results in a 41 amino acid deletion, was significantly associated with lack of remission (OR=0.18, P=0.02) and lack of response (OR=0.26, P=0.03) following 2nd switch treatment. A cytosine deletion 16 base pairs from the start of exon 8 in CREB1 was found more frequently in remitters and responders to 2nd switch antidepressant drug therapy, although these differences failed to reach significance. Polymorphisms detected BDNF (G196A) and CREBBP (T651C) did not appear to influence antidepressant response.
Conclusions These results suggest that inheritance of the GNB3C825T allele may significantly influence antidepressant response and emphasises the potential importance of polymorphisms in genes in signalling cascades activated by commonly prescribed antidepressants.

• 出版日期2007-3
• 单位河北医科大学