Department of Pharmacology, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576 104, India.
Department of Pharmacology, RAK College of Medical Sciences, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Eur J Clin Pharmacol. 2020 Jun;76(6):807-814. doi: 10.1007/s00228-020-02866-4. Epub 2020 Apr 6.
Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder.
A total of 148 depressive patients receiving escitalopram 10-20 mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA.
Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, LL haplotypes, and 2 L functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous L carriers compared with other groups.
Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LL haplotypes being the predictors of better treatment response.
种族在决定 5-羟色胺转运体基因多态性与选择性 5-羟色胺再摄取抑制剂(SSRIs)治疗反应之间的关联方向方面起着关键作用。本研究探讨了 5HTTLPR 和 5HTTLPR-rs25531 多态性与南印度重度抑郁症患者接受依地普仑治疗反应的关系。
共纳入 148 例接受依地普仑 10-20mg/d 治疗的抑郁患者,对 5HTTLPR 和 rs25531 多态性进行基因分型。采用 17 项汉密尔顿抑郁量表(HDRS-17)、蒙哥马利-阿斯伯格抑郁评定量表(MADRS)和临床总体印象量表(CGI)在基线和 4、8 和 12 周时进行临床评估。在第 12 周结束时,根据 HDRS17 和 MADRS 评分将患者定义为反应者和非反应者。采用卡方检验和逻辑回归分析探讨基因型对治疗反应的影响。采用 Student's t 检验或单因素方差分析比较不同组间的连续变量。
在 148 例研究对象中,65 例(43.9%)为反应者,83 例(56.08%)为非反应者。我们观察到 LL 基因型、LL 单倍型和 2L 功能组与依地普仑更好的治疗反应之间存在显著(p 值<0.001)关联。与其他组相比,LL 基因型和纯合 L 携带者的 HDRS17 和 MADRS 评分从基线下降更显著(p 值<0.001)。
结果表明,5HTTLPR 和 rs-25531 多态性可能影响南印度人群中抑郁患者的依地普仑治疗反应,LL 基因型和 LL 单倍型是更好治疗反应的预测因子。