Effect of basic fibroblast growth factor (FGF2) gene polymorphisms on SSRIs treatment response and side effects.
Antidepressant response usually appears in 2 to 4 weeks and 30-40% of patients do not show a significant response although biochemical changes of monoaminergic system occur within hours after administration. Genetic factors could play a role in this process and genes involved in synaptic plasticity and neurogenesis are possible candidates. In fact, antidepressants and electroconvulsive therapy increase basic fibroblast growth factor (FGF2) and the rs1449683C/T polymorphism within this gene has been found to be a predictor for both an elevated mRNA and protein level of FGF2. Therefore we examined the possible association of rs1449683C/T and a panel of tagging SNPs in SSRI efficacy and side effects in 144 Japanese major depressive subjects followed for 6 weeks. We observed a significant association of rs1449683T (p=0.010) and rs308393C (p=0.029) variant carriers toward a better response to SSRI and of rs1048201 with higher frequency of drop out due to side effects (p=0.010), independently from clinical variables. Furthermore the rs308447T-rs308393C-rs1449683T haplotype was associated with higher response rate (p=0.012) while the rs1048201T-rs3747676T haplotype was significantly associated with higher dropped out rate (p=0.015). In conclusion, this is the first study investigating the association of antidepressant response and intolerance with FGF2 variants. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response.
Kato
Masaki
M
Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. katom@takii.kmu.ac.jp
Okugawa
Gaku
G
Wakeno
Masataka
M
Takekita
Yoshiteru
Y
Nonen
Shinpei
S
Tetsuo
Shinji
S
Nishida
Keiichiro
K
Azuma
Junichi
J
Kinoshita
Toshihiko
T
Serretti
Alessandro
A
D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006239:Haplotypes; D006801:Humans; D010352:Patient Dropouts / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D016222:Fibroblast Growth Factor 2; D017367:Selective Serotonin Reuptake Inhibitors