Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder.
Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found to affect the expression and function of HTR1A. In fact rs6295C/G is in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than or together with the synonymous rs6295C/G. In the present study we examined the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression subjects followed for 6 weeks. We observed a significant association of better response to antidepressant in rs10042486C/C (P < 0.0001), rs6295G/G (P < 0.0001) and rs1364043T/T (P = 0.018) genotype carriers (minor allele homozygotes), independently from clinical variables. Furthermore minor allele homozygous carriers in all these three SNPs were associated with treatment response by various assessment such as HAM-D score change over time (P = 0.001), week 2 (P < 0.0001), 4 (P = 0.007), and 6 (P = 0.048) as well as response rate (P = 0.0005) and remission rate (P = 0.004). We also pointed out the genotyping mis-definition of rs6295C/G in the previous four articles. In conclusion, this is the first study that reports a significant association of antidepressant response with rs10042486C/T and rs1364043T/G variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.
Kato
Masaki
M
Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. masaki.kato@unibo.it
Fukuda
Tsuyoshi
T
Wakeno
Masataka
M
Okugawa
Gaku
G
Takekita
Yoshiteru
Y
Watanabe
Syunsuke
S
Yamashita
Megumi
M
Hosoi
Yuka
Y
Azuma
Junichi
J
Kinoshita
Toshihiko
T
Serretti
Alessandro
A
D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D018687:Antidepressive Agents, Second-Generation; D017931:DNA Primers; D044282:Receptor, Serotonin, 5-HT1A; D017367:Selective Serotonin Reuptake Inhibitors