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Neuropsychobiology. 2005;52(3):155-62. Epub 2005 Aug 25.

Serotonin receptor 2A gene polymorphism (-1438A/G) and short-term treatment response to citalopram.

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Pharmacogenomic Research Center for Psychotropic Drugs, Korea University, Seoul, Korea.


The 5-HTR2A gene is a candidate gene for influencing the clinical response to antidepressant treatment. The purpose of this study was to determine the relationship between the -1438A/G polymorphism in the 5-HTR2A gene and the response to citalopram in a Korean population with major depressive disorder (MDD). Citalopram was administered for 4 weeks to the 71 patients who completed this study. We found significant differences in genotype, allele, and carrier distribution between the normal group and MDD patients (genotypes: chi(2) = 6.473, d.f. = 2, p = 0.039; alleles: chi(2) = 5.589, d.f. = 1, p = 0.018; OR = 0.618, 95% CI = 0.414-0.922; allele carriers: chi(2) = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249-0.879). The frequency of the -1438G allele was much higher in MDD patients than in the normal group (allele carriers: chi(2) = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249-0.879). There were also significant differences in response to citalopram according to the -1438A/G variation of 5-HTR2A in MDD patients. The group of remitters carried a higher frequency of the GG allele than of the AA and AG alleles. More of nonremitters carried the A allele than were without it (genotype: chi(2) = 8.016, p = 0.018; allele carrier: chi(2) = 4.512, p = 0.034; OR = 0.324, 95% CI = 0.112-0.936). The response to citalopram differed with the -1438A/G polymorphism genotype and allele carriers. The -1438G/-1438G genotype appeared to be associated with a better response to citalopram, with especially the G allele being related to core depressive symptoms and psychic anxiety improvement (p<0.05). These results suggest that the G allele of the -1438A/G polymorphism in the 5-HTR2A gene is associated with MDD, and that patients with -1438G/-1438G have a better response to citalopram treatment than patients with -1438A/-1438A or -1438A/-1438G.

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