Potential Link between T102C Polymorphism in the Serotonin Receptors (5-HT2A) Gene and Treatment Response of Risperidone on Schizophrenia

BACKGROUND: Schizophrenia affects 1% of population and its molecular etiology remains enigmatic despite enormous study. Approximately one-third of patients failed to respond with treatment. The 5-HT2A receptor appears to be one of important site of action of atypical antipsychotic drugs. It also has been suggested that the T102C gene polymorphism alters promoter activity and expression of 5-HT2A receptors and might be responsible for the associations with the efficacy of typical antipsychotics. AIM: In this study, we aimed to evaluate the potential link between T102C polymorphism in the Serotonin Receptors (5-HT2A) and their response to risperidone. METHODS: We studied 100 schizophrenia patients and 100 healthy volunteers as a comparison of 5-HT2A receptors gene polymorphism distribution, which were all Indonesian. The peripheral blood samples were obtained from all participants. The patients assessed by Positive and Negative Scale (PANSS) and Clinical Global Impression Scale (CGI) when admitted to the hospital. Clinical improvements then assessed 5 times in 4 weeks (when transferred to sub-acute ward, at the 1st, the 2nd, the 3rd, and the 4th week). To analyze the T102C polymorphism of 5-HT2A receptor gene, we used an allele specific polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In this study, there were three various polymorphisms of T102C in the serotonin receptor (5-HT2A) gene: T/T, C/C, and T/C. The patients who had homozygous for T/T genotypes were found to give better improvement to risperidone than the patients who were C/C and T/C genotypes (P:0.001). Moreover, the patients with C allele genotype T/C and C/C had minimal response (P:0.001). We found no significant difference distribution of genotypes between schizophrenia patients and healthy volunteers (P:0.498). CONCLUSION: Our result supported that there was a potential link between T102C polymorphism in the serotonin receptor (5-HT2A) gene and treatment response of risperidone. It suggested the importance of genetic screening such as examination of the Serotonin Receptor 5-HT2A (T102C) gene polymorphism to be performed to optimize therapeutic strategies with antipsychotic.

RELATIONSHIP BETWEEN THE ALLOY FREQUENCY OF THE T102C POLYMORPHISM OF THE 5HT2A GENE WITH ANTHROPOMETRIC AND CARDIOMETABOLIC MEASURES

Obesity is a disease characterized by excessive body fat. Among the neurobiological factors associated with obesity, the serotonergic system stands out. The neurotransmitter of these circuits is serotonin (5-HT). Decreased levels of 5-HT have been linked to increased desire to ingest sweets and carbohydrates. This study aims to verify the relationship of the 5HT2A T102C gene polymorphism with obesity and anthropometric parameters. Blood samples and anthropometric data were collected from 150 volunteers, divided between the control and obese groups. The results showed that for individuals with diastolic pressure (p = 0.3681), Estimated Mean Glycemia (GMe) (p = 0.0228) and Homeostatic Model Assessment (HOMA-IR-IR) (p = 0.001) all altered, a higher frequency of C alleles was observed. For normal GMe (p = 0.0270), a higher frequency of the T allele was observed. There was no difference for the allele distribution between the normal and altered groups for the parameters of Triglycerides, HDL cholesterol, total cholesterol, glycated hemoglobin and Insulin. The distribution of the alleles between the groups, normal diastolic pressure (p = 0.3681) and HOMA-IR (p = 0.9203) groups presented no difference. From the genotypic analyzes of the T102C polymorphism of the 5HT2A gene, it was possible to demonstrate a relationship between the presence of the C allele with biochemical and anthropometric markers related to obesity and hypertension.

Clinical and genetic predictors of the severity and activity of paranoid schizophrenia

Clinical symptoms, course and outcomes of paranoid schizophrenia are polymorphic. Reliable predictors of severity and activity of schizophrenic process could provide clinicians important prognostic information for adequate and timely implementation of therapeutic and rehabilitative measures. Overall, 206 patients with paranoid schizophrenia were examined. Clinical predictors were collected from hospital records and interviews. BDNF gene Val66Met polymorphism (rs6265 G>A), DRD2 gene C939T polymorphism (rs6275C>T) and 5-HTR2A gene T102C polymorphism (rs6313 T>C) were studied as potential markers of prognosis for paranoid schizophrenia. Results of research testify that the DRD2 gene C939T polymorphism and 5-HTR2A gene T102C polymorphism cannot be used as predictors of the severity and activity of paranoid schizophrenia. The MetMet genotype of BDNF gene Val66Met polymorphism can be used as marker of favorable prognosis for paranoid schizophrenia. Schizoid, epileptoid, psychasthenic and conformal accentuation of personality in the premorbid, early onset of psychosis, paranoid and hallucinatory-paranoid variants of onset predicted more expressed severity of paranoid schizophrenia. These prognostic factors can be taken into account in clinical practice.Disclosure of interestThe authors have not supplied their declaration of competing interest.