Genetic Polymorphism of the Serotonin Transporter Gene,SLC6A4rs16965628, Is Associated with Obsessive Compulsive Disorder

Abstract

Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive ideas and compulsive behaviors. Genetic studies have centered on candidate genes involved in OCD etiology related to serotonergic and dopaminergic systems. In this study, the relationship between cathechol-O-methyltransferase (COMT) -287A/G (rs2097063), serotonin transporters 5-HTTLPR I/D, and SLC6A4 rs16965628 polymorphisms in 80 OCD patients and 100 healthy controls was determined. Patients and controls were genotyped for COMT rs2097063 and SLC6A4 rs16965628 polymorphisms by real-time polymerase chain reaction (PCR). The 5-HTTLPR I/D polymorphism was genotyped using PCR and agarose gel electrophoresis. Severity of symptoms was checked with a Yale-Brown Obsession Compulsion Scale (Y-BOCS). When the OCD group and controls were compared, no significant difference was found between COMT -287A/G (rs2097063), 5-HTTLPR I/D polymorphisms, and OCD. However, a significant difference was found between 5-HTT rs16965628 polymorphism and OCD (p=0.025, OR=3.43, 95% CI 1.41-10.35). In addition, the G allele frequency was found to be higher for rs16965628 in the OCD group. No significant difference was observed between COMT -287A/G (rs2097063), SLC6A4 rs16965628, and 5-HTTLPR I/D polymorphisms and Y-BOCS scores (p>0.05). There was also lack of correlation between Yale-Brown scores and gender of OCD patients. On the other hand, combined genotypes of SLC6A4 rs16965628 GG+GC were found to be risk factors for OCD development (p=0.02, OR=3.464; 95% CI 1.214-9.883) in logistic regression analysis adjusted for age and gender. Our findings suggest that subjects carrying the G allele of rs16965628 have genetic susceptibility to OCD. These data are the first to suggest that polymorphism in serotonin transporter (rs16965628) is associated with the development of OCD in the Turkish population.

Monoamine abnormalities in the SAPAP3 knockout model of obsessive-compulsive disorder-related behaviour

“…Furthermore, symptom exacerbation generally occurs when targeting receptors that negatively regulate presynaptic serotonin release [20,21], suggesting that deficient serotonin signalling contributes to OCD. In addition, associations of serotonin transporter gene polymorphisms with OCD [22][23][24][25][26][27][28] have led to speculation that OCD is associated with a hyposerotonergic state. However, many inconsistencies have made it difficult to isolate specific abnormalities within the serotonergic system.…”

“…These preclinical data may seem somewhat at odds with some clinical data. For instance, the utility of SRIs in treating OCD symptoms [19,64], decreased serotonin transporter availability [28,31,[65][66][67][68][69], and associations of polymorphisms of the genes encoding serotonin transporter [22][23][24][25][26][27][28] and serotonin 2A receptor [23] proteins with OCD have led to speculation that OCD is associated with a hypo-serotonergic state. However, it is important to note that the serotonin hypothesis has mixed support [1].…”

Catechol-O-Methyltransferase Val158Met and brain-derived neurotrophic factor Val66Met gene polymorphisms in paraphilic sexual offenders

“…COMT has also a role in drug metabolism including catechol used for the treatment of many diseases such as asthma and Parkinson's disease. [12131415] The monoamines, epinephrine, norepinephrine, serotonin, and tyramine, may play a role in the pathophysiology of paraphilias. These neurotransmitters are neuromodulators having effects on memory, motivational behavior, appetite, and sexuality of people.…”

SCL6A4 polymorphisms rs25533 and I425V: Association with obsessive–compulsive disorder and its treatment response in Iranian patients

“…Selective serotonin reuptake inhibitors (SSRIs) are effective in the OCD treatment [4,5]. Many studies have tried to search for the genes in the serotonergic systems which might be involved in the augmented predisposition to OCD [6][7][8]. One of the candidate genes is the serotonin transporter gene called SLC6A4, mapped to chromosome 17q11.1-q12 [9][10][11][12][13][14][15].…”

“…Different single nucleotide polymorphisms (SNPs) and variable number tandem repeats (VNTR) in 5-HTTLPR (5-HTT length polymorphic region) have been investigated as associated factors with OCD [17] and other mental disorders such as depression [18,19], autism [2], schizophrenia [20], Alzheimer [21], addiction [22] and aggression and antisocial behavior [23]. The investigated factors including rs2020930 and rs1487971 [2], rs25531 [5] rs16965628 [6], rs25532 [24], STin2 [25] are located both in coding or non-coding regions (e.g. regulatory promoter) of the gene.…”