Association of serotonin receptor 2a haplotypes with obsessive–compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study

Abstract

IntroductionObsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated.Patients and methodsAssociation analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP.ResultsThe results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders.ConclusionHTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation.

Impact of brain-derived neurotrophic factor Val66Met polymorphism and response to escitalopram or paroxetine in obsessive–compulsive disorder

“…We did not explore interactions between the BDNF gene and other gene variants, such as 5-HTTLPR and 5-HT2A rs6311, which have been associated with drug response in OCD. 25,26 It is also important to consider the possible role of clinical factors and environment-gene interactions, which could contribute to treatment response. Given these reasons, the interpretation of the results should be cautious and the genetic modulation of pharmacological response according to OC symptom dimensions needs to be further addressed in future studies.…”

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

“…However, other studies failed to observe these associations (Frisch et al, 2000;Gomes et al, 2018;Nicolini et al, 1996;Plana et al, 2019;Sina et al, 2018). OCD associations with rs6313 (Taylor, 2013), rs6305, and rs6308 polymorphisms (Noh et al, 2017), also considering early-onset (Mas et al, 2014), or symptoms severity (Tot et al, 2003), were reported.…”

“…OCD associations with rs6313 (Taylor, 2013), rs6305, and rs6308 polymorphisms (Noh et al, 2017), also considering early-onset (Mas et al, 2014), or symptoms severity (Tot et al, 2003), were reported. However, different studies did not report any association with these variants (Di Nocera et al, 2014;Gomes et al, 2018;Hemmings et al, 2003;Lochner et al, 2004;Miguita et al, 2011;Nicolini et al, 1996;Sina et al, 2018). The majority of studies conducted on HTR2C and HTR1B genes failed to demonstrate a direct link with the disorder (Camarena et al, 2004;Cristina Cavallini et al, 1998;Di Bella et al, 2002;Dickel et al, 2007;Frisch et al, 2000;Hemmings et al, 2003;Plana et al, 2019;Taylor, 2013;Walitza et al, 2004).…”

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders

“…Currently, several pharmacogenetic approaches using hypothesis-free GWAS have been conducted into the association between candidate genes and drug response in OCD patients (Di Bella et al, 2002;Denys et al, 2007;Van Nieuwerburgh et al, 2009;Miguita et al, 2011;Grünblatt et al, 2014;Zai et al, 2014;Umehara et al, 2015;Mas et al, 2016;Qin et al, 2016;Umehara et al, 2016;Taj et al, 2018;Lisoway et al, 2018;Sina et al, 2018;Abdolhosseinzadeh et al, 2019a,b;Alizadeh et al, 2019). The candidate genes investigated belong to: (1) pharmacokinetic regulating genes, such as the CYP450 liver enzymes such as CYP2D6 and CYP2C19;…”