The relationship between the serotonin 2A receptor gene -1438A/G and 102T/C polymorphisms and citalopram/sertraline-induced nausea in major depressed patients.

OBJECTIVE: The aim of the present study was to determine the relationship between the polymorphisms of -1438A/G and 102T/C in the 5-HT2A receptor (HTR2A) gene and nausea/vomiting as a side effect induced by sertraline (SERT) or citalopram (CIT) in patients with major depressive disorder. METHODS: A total of 128 patients were enrolled, 63 patients received CIT, whereas 65 patients were treated with SERT. Nausea/vomiting were assessed with the UKU Side-effects Rating Scale at baseline and at the end of the second and fourth weeks. Polymerase chain reaction-restriction fragment length polymorphism technique was employed to determine genetic differences. RESULTS: We have found that, in the patients treated with CIT, there was a nominally significant difference in the genotypic distribution associated with -1438A/G polymorphism between patients with and without nausea (X2  = 6.15, p = 0.041). Moreover, logistic regression analysis revealed a significant association between nausea/vomiting as a side effect and -1438A/G polymorphism. That is, patients with the G allele were at a higher risk for developing nausea/vomiting (p = 0.044, odds ratio = 2.213). The 102T/C polymorphism in the HTR2A gene had no significant effect on the nausea/vomiting as a side effect among participants treated with either CIT or SERT. CONCLUSION: The present study suggests the association of the HTR2A gene -1438A/G polymorphism with nausea/vomiting as a side effect related to CIT treatment.

Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients.

BACKGROUND: Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. OBJECTIVE: This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (-3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. SETTING: Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. METHODS: CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; -3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. MAIN OUTCOME MEASURE: The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. RESULTS: Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. CONCLUSION: CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy.

Allele and genotype frequencies of CYP2B6 in a Turkish population.

Increasing interest in cytochrome P450 2B6 (CYP2B6) genetic polymorphism was stimulated by revelations of a specific CYP2B6 genotype significantly affecting the metabolism of various drugs in common clinical use in terms of increasing drug efficacy and avoiding adverse drug reactions. The present study aimed to determine the frequencies of CYP2B6*4 CYP2B6*5, CYP2B6*6, CYP2B6*7 and CYP2B6*9 alleles in healthy Turkish individuals (n = 172). Frequencies of three single nucleotide polymorphisms were 516G>T (28%), 785A>G (33%), and 1459C>T (12%). The frequencies of CYP2B6*1, *4, *5, *6, *7, and *9 alleles were 54.3 (95% CI 49.04-59.56), 6.4% (95% CI 3.81-8.99), 11% (95% CI 7.69-14.31), 25.3% (95% CI 20.71-29.89), 0.87% (95% CI -0.11-1.85) and 2.0% (95% CI 0.52-3.48), respectively. Allele *6 was more frequent (25.3%) than the other variant alleles in Turkish subjects. The frequencies of CYP2B6*4, *5, *6, *7, and *9 alleles were similar to European populations but significantly different from that reported for Asian populations. This is the first study to document the frequencies of the CYP2B6*4, *5, *6, *7, *9 alleles in the healthy Turkish individuals and our results could provide clinically useful information on drug metabolism by CYP2B6 in Turkish population.