The polymorphism of the serotonin-2A receptor T102C is associated with age

Epidemiological investigations suggest that T102C polymorphism of gene 5-HT2A may be associated with mean life span because diseases and behaviors related to this polymorphism, such as schizophrenia, suicide, aggression, and addiction, may potentially shorten mean life span. A sample of 687 individuals without previous neuropsychiatric disease was genotyped and separated into 3 groups according to their gender and age: 14-45 years old, 46-64 years old and 65-100 years old. Molecular genotyping was performed using the technique of polymerase chain reaction followed by restriction fragment length polymorphism using HpaII restriction enzyme. 5-HT2A genotype frequencies were: TT = 21.5 percent (148), CC = 16.6 percent (114) and TC = 61.9 percent (425) and allele frequencies were T = 52.5 percent and C = 46.5 percent. Significant differences were found between mean age of the TT genotype carriers (60.27 ± 12.60 years) and TC genotype carriers (56.80 ± 13.18 years) of T102C polymorphism of gene 5-HT2A (P = 0.026) as well as the age groups (P = 0.012). Carriers of genotype TT were older than the other two genotypes, whereas carriers of genotype CC had an intermediate age compared with TT and CC subjects. The present results demonstrate an association between T102C polymorphism of gene 5-HT2A and age. Our results suggest that T102C polymorphism of gene 5-HT2A is associated with mean life span, and thus this gene becomes a possible candidate for the group of adaptive genes to meat consumption proposed in the literature. Further studies should be conducted in order to elucidate this association.

Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

The regulation of bladder function is influenced by central serotonergic modulation. Several genetic polymorphisms related to serotonin control have been described in the literature. T102C polymorphism of the serotonin receptor 2A gene (5-HT2A) has been shown to be associated with certain diseases such as non-fatal acute myocardial infarction, essential hypertension, and alcoholism. In the present study, we examined the association between 5-HT2A gene polymorphism and urinary incontinence in the elderly. A case-control study was performed in 298 elderly community dwellers enrolled in the Gravataí-GENESIS Project, Brazil, which studies gene-environmental interactions in aging and age-related diseases. Clinical, physical, biochemical, and molecular analyses were performed on volunteers. 5-HT2A genotyping was determined by PCR-RFLP techniques using the HpaII restriction enzyme. The subjects had a mean age of 68.05 ± 6.35 years (60-100 years), with 16.9 percent males and 83.1 percent females. The C allele frequency was 0.494 and the T allele frequency was 0.506. The CC genotype frequency was 21.78 percent, the CT genotype frequency was 55.24 percent and the TT genotype frequency was 22.98 percent. We found an independent significant association between the TT genotype (35.7 percent) and urinary incontinence (OR = 2.06, 95 percentCI = 1.16-3.65). Additionally, urinary incontinence was associated with functional dependence and systolic hypertension. The results suggest a possible genetic influence on urinary incontinence involving the serotonergic pathway. Further investigations including urodynamic evaluation will be performed to better explain our findings.

Association Study between 5-HT2A Receptor and DRD3 Receptor Gene Polymorphism and Clinical Response to Atypical Antipsychotics in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: This study was performed based on the hypothesis that the interindividual differences in clinical response to atypical antipsychotics might be associated with serotonin 2A receptor(5-HT2A) gene and(or) dopamine D3 receptor(DRD3) gene polymorphisms. METHODS: Seventy-five patients(39 men, 36 women) who met DSM-IV criteria for Schizophrenia at the Asan Medical Center were selected for the analysis of the medical records and subsequent interview. A written informed consent was obtained prior to the study and the privacy protection was kept throughout the course. Clinical Global Impression(CGI) Scale was applied after 4 weeks of treatment to assess the response to atypical antipsychotics. All patients in this study were administered olanzapine(n=39), risperidone(n=52) or clozapine(n=4). According to CGI scale, the patients were classified in 7 groups ; very much improvement ; much improvement ; minimal improvement ; no change ; minimal worsening ; much worsening ; very much worsening. The first and second groups were regarded as responders while the other groups were non-responders. Patients were genotyped for 5-HT2A by PCR(Msp I) for detection of T102 and C102 alleles. And they were also genotyped for DRD3 Ser9Gly polymorphism by PCR(Bal I). We conducted the statistical analyses to detect association between responders and non responders with chi-square tests. RESULTS: The patients who were shown no or minimally improved patients were sorted to non-responders(n=42, men 24, women 18) and the other patients shown much or very much improved were grouped as responders(n=33, men 15, women 18). The differences in demographic variables(age, sex), age of onset, and duration of illness were not statistically significant between the two groups. T102 allele is more frequent in non-responders(56.0%) than responders(45.5%), however, this difference is not statistically significant(p=0.20). Gly9 allele is near equal between non-responders and responders (65.5%, 65.2%). Genotype frequencies of the two groups also is not a statistically significant for 5-HT2A T102C(p=0.28) and DRD3 Ser9Gly(p=0.90). CONCLUSION:These results do not show significant associations among 5-HT2A gene, DRD3 gene and clinical response to atypical antipsychotics. On the assumption that responses to atypical antipsychotics are mediated by these two receptors, we can draw two possibilities. First, 5-HT2A and DRD3 genes may not be the functional variants related with responses to atypical antipsychotics. Second possibility is that the unknown variations which might be in linkage disequilibrium with the 5-HT2A T102C polymorphism and DRD3 Ser9Gly polymorphism may be associated with the response to atypical antipsychotics in schizophrenia. However, it is possible that the small number of subjects and ethnic difference of allele frequency of marker polymorphism could induce false negative results.

Association between Schizophrenia and the T102C Polymorphism of the 5-HT2A

The 5-HT2A receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has 5-HT2A antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of 5-HT2A receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.

An Association Stufy of the 5HT2A/T102C Polymorphism with Schizophrenia and Clinical Subtype / 신경정신의학

OBJECTIVES: Family, twin and adoption studies indicate that genetic factors play a crucial role in the etiology of schizophrenia. However, mode of inheritance of schizophrenia is uncertain, and genes for schizophrenia have not yet been identified despite extensive studies due to the complexity of the genetics of schizophrenia. Currently, 5HT2A receptor gene has attracted considerable interest as a susceptibility gene of schizoph,enia since the 5HT2A receptor has been known as one of the major target sites of atypical neuroleptics. We conducted an association study of T102C polymorphism in the 5HT2a receptor gene in Korean schizophrenic patients using PCR-RFLF method. METHODS: Two hundered and fifty biologically unrelated schizoprenic patients meeting DSM-III-R criteria from Kangnam St. Mary's Hospital affiliated with Catholic University of Korea were recruited for our study. The patient group consisted of 123 male and 127 female subjects, aged 30.1+/-9.3years. The controls were volunteers for DNA library of Kangnam St. Mary's Hospital withoyt family history of psychiatric or neurologic illness. The control group consisted of 124 males and 112 females, aged 23.6+/-3.7year. Amplified genomic DNA was digested by MspI. The significance of genetic association of the polymorphism was estimated by the logisitc regression anlysis and ANOVA using SPSS 7.5. RESULT: The allele frequencies and the genotypic distribution 5HT2a receptor gene were not significantly different between the patient and control group. In addition the allele frequencies and the genotypes of 5HT2a receptor gene were not significantly associated with subtype of schizophrenia. However, negative symptom score according to genotype show significant differenence(F=3.828 df=2 P=0.023). CONCLUSION: It is suggested that even if the development and subtype of schizophrenia may not beassociated with T102C polymorphism of 5HT2A receptor in Korean population, T102C polymorphism may be associated with the severity of negative symptom.