Biological and Pharmacogenomics Bases of Gastrointestinal and Some Long-Term Selective Serotonin Reuptake Inhibitors-Induced Adverse Effects

Abstract

Patients being treated with SSRIs who experience intolerable Adverse Effects (AEs) have a penchant for discontinuing treatment, inevitably jeopardizing any probability for treatment response. This study aims to identify the Single Nucleotide Polymorphisms (SNPs) that are associated with certain AEs of SSRI treatment in Major Depression Disorder (MDD). Patients with the short (SS) genotype (44 base pair deletion) and those with the long along with guanine substitution (LgLg - 44 base pair insertion with rs25531- guanine substitution variant) of the serotonin transporter gene (STG) have substantially been reported with a higher incidence of AEs to SSRI. While variants of glutamate receptor ionotropic genes have been found to be linked with different domains of sexual dysfunction, polymorphisms of 5-HT2A gene - rs6311 (G > A), the long allele (L) of STG, rs6295 (C > G) polymorphism of HTR1A and polymorphism rs1160351 (A > C) of MAM domain-containing glycosyl-phosphatidyl inositol anchor 2 (MDGA2) gene have also been found to be associated with sexual dysfunction. The rs4680 (G>A; Val > Met) polymorphism of catechol-O-methyltransferase (COMT), AA genotype of rs18532 polymorphism of tryptophan hydroxylase, the rs6318 (C > G) polymorphism of the serotonin receptor 2C (HTR2C), and S allele of STG were found to be associated with weight gain following SSRI treatment. The sanctity of these results is limited by the inability of some researchers to replicate these association findings. This review highlights a number of polymorphisms associated with some of the key AEs encountered in SSRI treatments. Standardized study designs in pharmacogenomic evaluations hold great promise for replication of association findings.