HTR1A polymorphisms are associated with the antidepressant response in patients with 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 for 5-HT1A gene (HTR1A) has been found to effect the expression and function of HTR1A In fact rs6295C/G was in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than the synonymous rs6295C/G. In the present study we examine the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression sample followed for 6 weeks. We observed the significant association of better response to antidepressant with rs10042486C/C (p<0.0001), rs6295G/G (p<0.0001) and rs1364043T/T (p=0.018) genotype carriers, that is mutant allele homozygote, independently from clinical variables. Furthermore mutant allele homozygote carriers in all these 3 SNPs was associated more solidly 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).In conclusion, this is the first study that reports the significant association of antidepressant response with rs10042486C/T and rs1364043G/T variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.