Major Depresif Bozukluğu Olan Türk Hastalarda 5-HTTLPR Polimorfizmin ve Sitalopram Yanıtı Arasındaki İlişkisi

Bu çalışmanın amacı, serotonin transporter geni bağlantılı polimorfik bölgenin (5-HTTLPR) genetik polimorfizmini ve bunun majör depresif bozukluğu olan Türk hastalarda sitalopram tedavisine yanıt ve tedavinin yan etkileriyle ilişkisini araştırmaktır. Çalışma, 4 ile 6 hafta boyunca 10-40 mg/gün sitalopram kullanmış 51 hastadan oluşmuştur. Klinik belirtiler 4 ve/veya 6 haftada 17 maddelik Hamilton Depresyon Derecelendirme (HAMD-17) ölçeği, Klinik Global İzlenim (KGİ) ve UKU Yan Etki Değerlendirme ölçekleri (UKU) ile değerlendirildi. 5-HTTLPRL/S polimorfizmi yavaşlama-polimeraz zincir reaksiyonu yöntemi ile belirlenmiştir. Elli bir hastanın, 13'ü (% 26) LL genotip, 21'i (% 41) LS genotip, 17'si (% 33) ise SS genotipli idi. S aleline karşı L allelin odds oranından dolayı, istatistiksel olarak anlamlı olmamasına rağmen L alleli daha iyi yanıt verme ile ilişkili görünmektedir. KGI-Şiddet ölçeği açısından, 6. haftada LS genotipe karşı LL genotipi daha yüksek riske sahipti (P<0.05). Öte yandan, bu kıyaslamının dışında 4. ve/veya 6. haftada genotip dağılımlarına göre KGİ-Şiddet ve İyileşme ve UKU ölçeklerinde önemli farklılık bulunmamaktadır. Ancak, bu bulguların daha fazla araştırılması ve doğrulanması gerekmektedir.The objective of this study was to investigate the relationship between the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response to citalopram treatment and side effects in Turkish patients with major depressive disorder. The study involved 51 patients who received 10-40 mg/day of citalopram for 4 to 6 weeks. Clinical symptoms were evaluated by the 17-item Hamilton Depression Rating (HAMD-17) scale, Clinical Global Impression (CGI) and UKU side effect rating scale (UKU) at weeks 4 and/or 6. The 5-HTTLPRL/S polymorphism was determined by slowdown-polymerase chain reaction method. Of the fifty-one patients, 13 (26%) were the LL genotype, 21 (41%) were the LS genotype, 17 (33%) were the SS genotype. L allele seems to be associated with better response due to odds ratio for L allele versus S allele despite statistically insignificant. In terms of CGI-Severity scale, The LL genotype versus the LS genotype had a higher risk at the week 6 (P&lt;0.05). On the other hand, apart from this comparison, there is no significant difference in CGI-Severity and Improvement and UKU scales according to the distribution of genotypes at week 4 and/or 6. However, these findings surely need further investigation and confirmation

Genotype and Allele Frequency of CYP3A4-392A > G in Turkish Patients with Major Depressive Disorder

OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382; ozguven, halise/0000-0002-9355-2757; Suzen, Sinan/0000-0003-1779-5850WOS: 000438973100013PubMed: 32454661Objectives: Genetic polymorphisms may help for individualized drug dosing and improved therapeutics. CYP3A4 is responsible for the metabolism of more than 50% of the commonly used drugs and metabolizes typical antipsychotic medications and antidepressant drugs. The objective of the study was to assess the genotype and allele frequencies of CYP3A4 -392A>G in Turkish patients with major depressive disorder receiving any SSRIs and to compare these results with the frequencies of other ethnic groups. Materials and Methods: Genotyping analyses of CYP3A4 -3921>G was conducted on 84 Turkish patients using the PCR-RFLP technique. Results: The allele frequencies were found as 0.982 (A) and 0.018 (G) for CYP3A4 -392A>G. The genotype frequencies were determined as 0.976 (AA), 0.012 (AG), and 0.012 (GG). The genotype frequencies were consistent with the Hardy-Weinberg equilibrium. Conclusion: The genotype and allele frequencies of CYP3A4 -392A>G were determined to be low in Turkish patients with major depressive disorder receiving SSRIs. Furthermore, the results of the study were compared with those of other ethnic groups and they displayed pronounced differences among other ethnic groups, especially black subjects.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S147]This work was supported by the Scientific and Technological Research Council of Turkey (Project: 109S147)

Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients

Suzen, Sinan/0000-0003-1779-5850WOS: 000536015300011PubMed: 31792367Sexual dysfunction (SD) is a troublesome adverse effect of selective serotonin reuptake inhibitors (SSRIs). A variety of mechanisms might be involved in the occurrence of SD but the exact mechanism is still not clear. Genetic variations among patients treated with SSRIs are strong determinants of intolerance and poor compliance. The present study aimed to determine the relationship between serotonin-2A receptor (HTR2A) gene -1438A/G and 102T/C polymorphisms, serotonin transporter gene (SLC6A4) 5-HTT-linked polymorphic region (5-HTTLPR) insertion/deletion variant and brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphisms and the occurrence of SD adverse effect in major depressive disorder patients treated with citalopram (CIT) or sertraline (SERT). The result from this investigation revealed that the -1438A/G and 102T/C polymorphisms appear to be associated with the SD induced by CIT. It was also demonstrated that patients receiving SERT, carrying T allele of HTR2A or L allele of 5-HTTLPR more likely to experience SD. Most important overall finding of the study is the combined effects of -1438A/G, 102T/C, and 5-HTTLPR polymorphisms. In a logistic regression model, the occurrence of SD increased with the number of risky alleles. As compared with subjects receiving SERT with few risky (<= 2) alleles, those with had 5-6 alleles had an increased SD risk. After all, according to these findings, -1438A/G, 102T/C, and 5-HTTLPR polymorphisms could be considered as promising pharmacogenetic biomarkers in CIT/SERT treatment in major depressive disorder (MDD) patients to avoid the occurrence of SD

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

ozguven, halise/0000-0002-9355-2757; Suzen, Sinan/0000-0003-1779-5850; OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382WOS: 000374326900029PubMed: 26830411Background 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