Association between serotonin 2A receptor gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients

Sexual 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 in...

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Bibliographic Details
Published in:The pharmacogenomics journal 2020-06, Vol.20 (3), p.443
Main Authors: Oz, Merve Demirbugen, Baskak, Bora, Uckun, Zuhal, Artun, Nazan Yuce, Ozdemir, Hatice, Ozel, Tugba Kizil, Ozguven, Halise Devrimci
Format: Article
Language:English
Subjects:
Brain-derived neurotrophic factor
Causes of
Citalopram
Complications and side effects
Drug therapy
Genetic aspects
Health aspects
Major depressive disorder
Receptors
Serotonin
Sertraline
Sexual disorders
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Summary:Sexual 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 ([less than or equal to]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.
ISSN:1470-269X
1473-1150
DOI:10.1038/s41397-019-0127-8