title: Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder.
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. masaki.kato@unibo.it
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.forename: Gaku
authors.initials: G
authors.lastname: Okugawa
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.forename: Syunsuke
authors.initials: S
authors.lastname: Watanabe
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hosoi
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: 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*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017931:DNA Primers; D044282:Receptor, Serotonin, 5-HT1A; D017367:Selective Serotonin Reuptake Inhibitors