5-HTTLPR-rs25531 and Antidepressant Treatment Outcomes in Korean Patients with Major Depression

Abstract Introduction Despite the ethnic differences in 5-HTTLPR (S allele relates to better antidepressant response in Korean and Japanese people, while L allele with better response in Caucasians), it is unclear whether 5-HTTLPR and its high expression locus rs25531 are interactively associated with antidepressant treatment outcome. We investigated the individual and interaction effects of these polymorphisms on antidepressant treatment outcomes in the Korean population. Methods A total of 464 Korean subjects with major depressive disorder completed 6 weeks of antidepressant monotherapy. Venous blood was extracted for genotyping 5-HTTLPR and rs25531 by polymerase chain reaction and DNA sequencing. We used logistic regression analyses to verify the main and interaction effects of 5-HTTLPR and rs25531 on response and remission after antidepressant treatment. Results After adjusting for covariates, the SS genotype of 5-HTTLPR was significantly associated with better treatment outcomes (p<0.001, odds ratio [OR] [95% confidence interval (CI)]=2.435 [1.551, 3.823] in response; p<0.001, OR [95% CI]=2.912 [1.730, 4.903] in remission), while G-containing genotype (AG+GG) of rs25531 was only associated with remission (p=0.034, OR [95% CI]=2.104 [1.058, 4.181]). The interaction effect of 5-HTTLPR and rs25531 on response and remission was insignificant (all p>0.05). Discussion Our findings suggest variations in allelic frequency and functionality of 5-HTTLPR and rs25531 among the different ethnicities. We found a minor advantage of rs25531 in achieving remission. However, there was no interaction effect with 5-HTTLPR.