RESUMO
BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a complex and chronic disorder characterized by recurrent thoughts and/or repetitive behaviors. Given the potent anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes related to serotonergic system may be well implicated in the etiopathogenesis of OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been previously associated with OCD. Additionally, the serotonin 2A receptor gene (HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have also been overrepresented among OCD patients. Therefore, the aim of this study is to evaluate the association of these three polymorphisms with OCD, through the examination of potential sources of heterogeneity in previous studies including age of onset, sex and symptom dimensions. METHODS: Polymorphisms were genotyped by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205 healthy controls from Brazil. RESULTS: Although we did not observe any statistically significant association between the HTR2A gene polymorphisms and OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more common among OCD patients as compared to health controls. Further, a significant association between the STin2.12 allele and OCD, as well as a dominant effect of the STin2.12 allele in OCD was seen. Of note, late-onset (>18years) OCD was significantly more often seen in association with homozygosis for STin2.12 allele. No significant associations were observed with different OCD symptom dimensions. CONCLUSION: Our results indicate an important influence of the STin2 polymorphism in OCD, but more studies are warranted to confirm these results.
Assuntos
Estudos de Associação Genética/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético/genética , Receptor 5-HT2A de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Brasil/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/epidemiologiaRESUMO
The etiology of OCD is largely unknown, but neuroimaging and pharmacological studies suggest that glutamatergic system plays a significant role on OCD development. We genotyped one polymorphism at GRIN2B (rs1019385) by real time Polymerase Chain Reaction in a sample of Brazilian Obsessive-Compulsive patients and healthy controls, and evaluated its influence on OCD. We found the T-allele and TT genotype to be significantly associated with OCD and ordering dimension. The T-allele was also significantly associated with checking. These preliminary results demonstrated that the GRIN2B gene may confer to some extent the susceptibility to OCD and its symptoms.
Assuntos
Alelos , Genótipo , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Adulto , Brasil , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Projetos Piloto , Adulto JovemRESUMO
Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan(®) or restriction mapping. We observed a statistically significant predominance of the Met low-activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted.