5-HT2A Receptor Gene Polymorphism Research Articles

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.

Identification of genetic correlates of response to Risperidone: Findings of a multicentric schizophrenia study from India.

Risperidone is most commonly used as an antipsychotic in India for treatment of schizophrenia. However, the response to treatment with risperidone is affected by many factors, genetic factors being one of them. So, we attempted to evaluate the association between dopamine D2 (DRD2) receptor, serotonergic (5HT2A) receptor and CYP2D6 gene polymorphisms and response to treatment with risperidone in persons with schizophrenia from North India. It was a multicentric 12-weeks prospective study, undertaken in patients diagnosed with schizophrenia according to International Classification of Diseases 10th revision, Diagnostic Criteria for Research module (ICD-10 DCR). Patients were treated with incremental dosages of risperidone. Nine gene polymorphisms from three genes viz. DRD2, 5-HT2A and CYP2D6 along with socio-demographical and clinical variables were analyzed to ascertain the association in response to risperidone treatment. The change in the Positive and Negative Syndrome Scale (PANSS) was used to measure the outcome. Significant differences in the frequencies of single nucleotide proteins (SNPs) rs180498 (Taq1D) and rs 6305 (C516T) polymorphisms were found amongst the groups defined according to percent decline in PANSS. The CYP2D6*4 polymorphism differed significantly when drop outs were excluded from analysis. Presence of DRD2 Taq 1 D2D2 and 5-HT2A C516T CT genotypes in patients were more likely to be associated with non-response to risperidone. Ser311Cys (rs1801028) mutation was absent in the North Indian patients suffering from schizophrenia.

Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality risk among Brazilian Amazon riparian elderly population.

Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.

Influence of occupational stress and 5-hydroxytryptamine 2A receptor gene polymorphisms on depression in workers in a thermal power plant

Objective: To investigate the association of occupational stress and 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphisms with depression. Methods: In November 2010, cluster sampling was used to select 589 workers in a thermal power plant as study subjects. Questionnaires were used to investigate demographic features and occupational stressors. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of T102C and A-1438G in 5-HT2A receptor gene in 589 workers. Results: High-level daily hassles (OR=3.013, 95%CI 1.642~5.530) , more negative emotion (OR=4.808, 95% CI 2.662~8.681) , more body needs (OR=1.890, 95% CI 1.034~3.453) , and severe role conflict (OR=1.815, 95% CI 1.002~3.288) were risk factors for depression, while high rewards (OR=0.424, 95% CI 0.226~0.796) was the protective factor against depression (all P<0.05). There were no significant differences in T102C genotype and allele distributions between the groups with and without depression (P>0.05) ; there was a significant difference in A-1438G genotype distribution between the groups with and without depression (χ2= 9.573, P<0.05) , while there was no significant difference in A-1438G allele distribution between these groups (P>0.05). The risk of depression in the workers with high-level daily hassles who carried TC genotype (OR= 4.473, 95% CI 1.161~17.238) or CC genotype (OR=5.176, 95% CI 1.367~19.593) of T102C was 4.473 and 5.176 times that in those with low-level daily hassles who carried TT genotype, and the risk of depression in the workers with more negative emotions who carried TC genotype (OR=5.667, 95%CI 1.204~26.673) or CC genotype (OR=8.114, 95% CI 1.747~37.677) of T102C was 5.667 and 8.114 times that in those with less negative emotion who carried TT genotype. The risk of depression in the workers with high-level daily hassles who carried AG genotype (OR=4.505, 95% CI 2.215~9.162) or GG genotype (OR=6.484, 95% CI 2.562~ 16.414) of A-1438G was 4.505 and 6.484 times that in those with low-level daily hassles who carried AA genotype, and the risk of depression in the workers with more negative emotion who carried AG genotype (OR= 4.877, 95%CI 2.326~10.223) or GG genotype (OR=9.090, 95%CI 3.491~23.673) of A-1438G was 4.877 and 9.090 times that in those with less negative emotion who carried AA genotype. The risk of depression in the workers with higher rewards who carried AG genotype (OR=0.152, 95%CI 0.074~0.310) or GG genotype (OR= 0.384, 95% CI 0.153~0.964) of A-1438G was 0.152 and 0.384 times that in those with lower rewards who carried AA genotype. Conclusion: Occupational stress is associated with the development of depression and interacts with 5-HT2A receptor gene polymorphisms.

Association between 5-hydroxytryptamine 2A receptor gene polymorphisms and susceptibility to occupational stress in oilfield workers

Objective: To investigate the association between 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphisms and occupational stress in oilfield workers. Methods: Cluster sampling was used to select 826 oilfield workers from January to August, 2013. The SNaPshot single nucleotide polymorphism (SNP) genotyping method was used to determine the genotypes of rs6313, rs1923884, and rs2070040 in 5-HT2A receptor gene, and the Occupational Stress Inventory-Revised Edition was used to analyze occupational stress in these workers. Results: There were no significant differences in occupational stress between groups with different individual characteristics (P>0.05 ) . As for the comparison of occupational stress scores between workers with different genotypes of each SNP of 5-HT2A receptor gene, the workers with CC and CT genotypes of rs6313 had significantly higher role boundary scores than those with TT genotype (P<0.05) , and the workers with CC genotype had a significantly higher vocational stress score than those with CT genotype (P<0.05) ; the workers with CT genotype of rs1923884 had a significantly higher occupational role score than those with CC genotype (P<0.05) and a significantly higher coping resources score than those with CC and TT genotypes (P<0.05) ; the workers with AG genotype of rs2070040 had a significantly higher vocational stress score than those with AA genotype (P<0.05) . The ordinal multinomial logistic regression analysis showed that workers with CT genotype of rs1923884 were susceptible to occupational stress (OR=1.56, 95%CI 1.10~2.20) . Conclusion: CT genotype of rs1923884 in 5-HT2A receptor gene may be associated with the susceptibility to occupational stress in oilfield workers.

Association of Polymorphisms within the Serotonin Receptor Genes 5-HTR1A, 5-HTR1B, 5-HTR2A and 5-HTR2C and Migraine Susceptibility in a Turkish Population.

ObjectiveMigraine, a highly prevelant headache disorder, is regarded as a polygenic multifactorial disease. Serotonin (5-HT) and their respective receptors have been implicated in the patogenesis.MethodsWe investigated the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor gene polymorphisms and their association with migraine in Turkish patients. The rs6295, rs1300060, rs1228814, rs6311, rs6313, rs6314, rs6318, rs3813929 (−759C/T) and rs518147 polymorphisms were analyzed in 135 patients with migraine and 139 healthy subjects, using a BioMark 96.96 dynamic array system.ResultsWe found no difference in the frequency of the analyzed eight out of nine polymorpisms between migraine and control groups. However, a significant association was found between the rs3813929 polymorphism in the promoter region of 5-HTR2C gene and migraine. Also, the allele of rs3813929 was more common in the migraine group.ConclusionThis result suggests that the 5-HTR2C rs3813929 polymorphism can be a genetic risk factor for migraine in a Turkish population.

Effect of a human serotonin 5-HT2A receptor gene polymorphism on impulsivity: Dependence on cholesterol levels

BackgroundImpulsivity is multidimensional: Low impulse control may result in behavioural disorders, but acting on the spur of moment may also be advantageous. Previous studies have shown negative associations between different facets of impulsivity and serotonergic function. Other investigations have found negative correlations between serum lipid levels and impulsivity. MethodsWe have investigated whether the functional polymorphism -1438A/G in the serotonin 5-HT2A receptor gene (HTR2A) is associated with impulsivity levels and whether there is any interaction with serum lipid levels. This analysis was based on data of the population-representative Estonian Children Personality Behaviour and Health Study at age 25. Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale. ResultsSubjects with the A/A genotype of the HTR2A -1438A/G polymorphism had higher scores of Maladaptive impulsivity, but not Adaptive impulsivity. In females, high LDL and total cholesterol levels increased the genotype effect. In males, in the highest quartile of total or LDL cholesterol the genotype effect was altered, with G/G homozygotes having the highest Maladaptive impulsivity levels. LimitationsOnly one cohort of the European Youth Heart Study (EYHS) was used in the current study and impulsivity measures were self-reported. ConclusionsOur results do not support the notion that low cholesterol levels universally lead to higher impulsivity, but it was found that high total and LDL cholesterol levels moderate the effect of the HTR2A gene promoter polymorphism. This suggests that future studies on impulsivity need to consider the interaction of serotonergic measures with the whole range of cholesterol levels.

Meta analysis on the relationship between 5-hydroxytryptamine 2A receptor gene polymorphism T102C and schizophrenia

Objective To assess the association of 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphism with schizophrenia by Meta analysis. Methods Literatures on the relationship between 5-HT2A receptor gene polymorphism T102C and the Chinese schizophrenia in EMBASE, PubMed, CBM, CNKI and Wanfang Med Online were taken as research objects.Screening the relevant data according to the included and excluded standard , then, Software of RevMan 5.0 was employed to do Meta analysis. Meanwhile, we inspect the literatures publication bias. Results Twelve literatures were included, collecting 4 728 individuals , enrolling 2 135 for the schizophrenia group and 2 593 for the control group.The research conforms to Hardy Weinberg equilibrium (all P>0.05). The Meta analysis results showed that there was no significant association between 5-HT2A receptor gene polymorphism and schizophrenia including the allele model, recessive model and codominant model genotypes(all P>0.05). The results of Dominant genetic model I2=45% with moderate heterogeneity, but we used subgroup analysis to remove the author Ni’s data , there were significant difference analysis (I2=9%, Z=2.01, P<0.05). Conclusions 5-HT2A receptor gene T102C site C allele is recessive genes, CC may be a healing factor, there needs evidence-based study provides further evidence. Key words: Schizophrenia; 5-HT2A; T102C; Meta analysis

Association of 5-HT2A receptor gene polymorphisms with gastrointestinal disorders in Egyptian children with autistic disorder.

Gastrointestinal disturbances (GID) are frequently reported in children with autism spectrum disorders (ASD). Recently, mounting evidence suggests that there may be a genetic link for autism with gastrointestinal disturbances. We aimed to investigate whether there were any association between the -1438A/G, 102T/C and His452Tyr polymorphisms of the serotonin 2A receptor gene (5-HT2A) in Egyptian children with ASD and GID. Eighty children with autistic disorder and 100 healthy control children were examined. -1438A/G, 102T/C and His452Tyr polymorphisms of 5-HT2A were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant increase of the G allele and the GG genotype of the -1438A/G polymorphism was observed in children with autism than control, but there were no significant differences in the frequencies either of the 102T/C genotype or His452Tyr genotype between the two groups. There was a significant increase of homozygote A allele of the -1438A/G and CC genotype of the 102T/C polymorphism in ASD children with GID. This study supports the possible involvement of the 5-HT2A receptor in the development of ASD and associated GID.

Effect of 5HT2A receptor gene polymorphism on lateral prefrontal cortex activation during empathy

Effect of 5HT2A receptor gene polymorphism on lateral prefrontal cortex activation during empathy

The assessment of the T102C polymorphism of the 5HT2a receptor gene, 3723G/A polymorphism of the NMDA receptor 3A subunit gene (GRIN3A) and 421C/A polymorphism of the NMDA receptor 2B subunit gene (GRIN2B) among cardiac surgery patients with and without delirium

ObjectiveThe studies regarding the role of genes polymorphism in development of postoperative delirium are extremely rare. Therefore, we investigated the potential association of polymorphism in 5HT2a receptor gene and N-methyl-d-aspartate (NMDA) receptor 3A and 2B subunits genes with postoperative delirium. MethodWe conducted a prospective, nested, case–control study. For analysis, 3723G/A (rs3739722) polymorphism in the GRIN3A gene, 421C/A (rs3764028) polymorphism in the GRIN2B gene and T102C (rs6313) polymorphism in the 5HT2A gene were selected. ResultsGenetic analysis confirmed that there were significant differences in genotype frequencies for 3723G/A between delirium patients and controls. No other significant associations were observed. Moreover, according to the multivariate conditional logistic regression analysis the presence of AG haplotype of GRIN3A gene was independently associated with postoperative delirium. ConclusionsThese findings suggest that the genetic variations of NR3A subunit of NMDA receptor may be a predisposing factor to delirium among the Polish population of cardiac surgery patients.

Association study of gene polymorphisms and depression with abnormal humor in traditional Uighur medicine

BackgroundAccording to the humor theory of Traditional Uighur Medicine (TUM), a same disease is classified into different abnormal humor types and corresponding methods are applied to treat the diseases according to the type of abnormal humor characteristics. To date the biological foundation of classification of diseases by humor theory has been little studied and the mechanism of action is still unclear. In the present study, we aimed to investigate the association between some related gene polymorphisms and depression with abnormal humor in TUM.Methods201 cases of depression patients in a Uighur population were divided into two groups as: 107 cases of depression patients with abnormal black bile (ABB), 94 cases of depression patients with none abnormal black bile (nABB), and 50 healthy people were served as control group. Venous blood was used to isolate DNA samples, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of single nucleotide polymorphisms (SNPs). Polymorphisms in the serotonin 2A (5-HT2A) receptor gene, brain derived neurotrophic factor (BDNF), serotonin 1A (5-HT1A) receptor gene were investigated in each groups, respectively.ResultsThe 5-HT2A A-1438G, 5-HT2A T102C, BDNF Val66Met, and 5-HT1A C-1019G gene polymorphisms showed significant association with ABB. However, no difference between nABB and controls was found for those genotype distribution and allele frequency. Moreover, the T102C and A1438G SNPs in the 5-HT2A receptor gene polymorphisms were in linkage disequilibrium. In addition, the OR associated with the combination of Val66Met-Val/Val genotype plus the presence of -1019C allele was 8.393 for ABB compared with controls (OR 8.393; 95% CI 1.807 ~ 38.991; P= 0.003). Moreover, the OR associated with the presence of -Met plus -1019C alleles was 12.194 for ABB compared with controls (OR 12.194; 95% CI 1.433 ~ 103.776; P= 0.005). The OR associated with the presence of -1438C/C plus Val/Val genotypes was 7.738 for ABB compared with controls (OR 7.738; 95% CI 1.566 ~ 38.241; P= 0.005).ConclusionIt was concluded that there were significant relationship between the gene polymorphisms and classification of depression with abnormal humor in TUM. The 5-HT2A A-1438G, 5-HT2A T102C, BDNF Val66Met, and 5-HT1A C-1019G gene polymorphisms might predict the incidence of depression with ABB.

Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being -1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between -1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for -1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the -1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169-4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879-4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787-1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737-1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the -1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.

Association of schizophrenia with T102C (rs6313) and 1438 A/G (rs6311) polymorphisms of HTR2A gene

The aim of this study is to investigate whether there were any associations between the T102C and 1438 A/G polymorphisms of the 5-HT2A receptor gene and schizophrenia. We conducted a case-control study of the T102C and 1438 A/G polymorphisms in Turkish patients. We compared genotypes and allele frequencies of T102C and 1438 A/G polymorphisms of 5-HT2A receptor gene in 102 patients with schizophrenia diagnosed, according to DSM-IV, and 107 healthy controls. Genotyping was performed by real-time polymerase chain reaction. We found no significant association between schizophrenia and genotypic or allele frequencies of HTR2A gene 102T/C (rs6313) and 1438 A/G (6311) polymorphisms. However, comparison of HTR2A gene 102 T/C and 1438 A/G polymorphisms in terms of genotypic and allele frequencies between the two patient groups, with or without a family history of schizophrenia, shows that T- and A-allele frequencies were significantly higher (p < 0.05) in the case group that has a history of schizophrenia in their family. In conclusion, our results do not support the hypothesis that the T102C and 1438 A/G polymorphisms in the 5-HT2A receptor gene are associated with schizophrenia, but further studies in a larger sample are needed.

Association of the 5-HT2A receptor gene polymorphisms with obstructive sleep apnea hypopnea syndrome in Chinese Han population

Conclusions: The -1438G/A polymorphism of 5-HT2A receptor gene may associate with obstructive sleep apnea hypopnea syndrome (OSAHS) in a Chinese Han population. Different genotypes of -1438G/A polymorphism may influence the ventilatory activity in response to hypoxia, and in turn the sleep breath status. Objective: This study was designed to assess the association of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene with OSAHS in a Chinese Han population. Methods: A total of 315 subjects (210 patients and 105 controls) were included for genetic analyses of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene. Results: Six single nucleoside polymorphism (SNP) sites were identified in the sequencing of the promoter and exons of the 5-HT2A receptor gene; however, genotypes and allele frequencies of the SNPs did not show significant differences between the patients and controls except the -1438G/A polymorphism. For SNP of -1438G/A, the A/A genotype was over-represented and the allele A was more frequent in the patients, while the G/A genotype was over-represented and the allele G was more frequent in the controls (p < 0.001, p = 0.005, respectively). In the patients, the A/A and G/A genotypes were over-represented in the subgroups with lowest nocturnal SaO2 (LSaO2) ≤75% and LSaO2 >75%, respectively (p = 0.006).

5-HT2A Receptor Gene Polymorphisms and Irritable Bowel Syndrome

The aim of the study was to investigate the potential association between single nucleotide polymorphisms of the 5-HT2A receptor gene and susceptibility to irritable bowel syndrome (IBS) in the Greek population. Serotonin [5-hydroxytryptamine (5-HT)] is the main mediator involved in the pathophysiology of IBS. Thus, genes implicated in 5-HT metabolism are good candidates for susceptibility to IBS. Two single nucleotide polymorphisms -1438 (G/A) and 102 (C/T) in the 5-HT2A receptor gene have been associated with the pathophysiology of IBS. One hundred twenty-four patients with IBS diagnosed according to the Rome III criteria and 238 healthy individuals were included in the study. The -1438 (G/A) and 102 (C/T) in the 5-HT2A receptor gene polymorphisms have been studied using the polymerase chain reaction based restriction fragment length polymorphism method. A genotype association was found between A allele and AA genotype of the -1438 (G/A) polymorphism and IBS (P=0.0037 and P=0.0064, respectively). Concerning the 102 (C/T) polymorphism, no significant association was found. This study suggests that the carriers of A allele of the -1438 (G/A) polymorphism of the 5-HT2A receptor gene have a high risk of IBS.

Interaction between two HTR2A polymorphisms and gender is associated with treatment response in MDD

The 5HT2A receptor gene (HTR2A) polymorphisms rs7997012 and rs6311 have in some earlier studies been associated with serotonin selective reuptake inhibitor (SSRI) treatment response in major depressive disorder (MDD), but the findings are inconsistent. The aim of the present study was to test for an association between two HTR2A polymorphisms (rs7997012 and rs6311), their interaction and the Montgomery and Åsberg Depression Rating Scale (MADRS) score change after ECT or SSRI treatment. The total number of patients was 218. All were treated in outpatient care. Of these, 119 subjects had treatment-resistant MDD and were treated with ECT and 99 were depressive patients treated with SSRI. Treatment response was assessed by MADRS. Patients scoring <8 on post-treatment MADRS were considered remitters. Neither rs7997012 nor rs6311 HTR2A polymorphism was significantly associated with MADRS score change alone, but the interaction between them and gender explained 14% of the variance in MADRS score change. The finding suggests an association between MADRS score change and interaction of HTR2A polymorphisms, rs7997012 and rs6311 and gender.

Role of 2 Common Variants of 5HT2A Gene in Medication Overuse Headache

The aim of the present study was to evaluate a possible involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption. Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month. Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Genotype-specific risks were estimated as odds ratios with associated 95% confidence intervals by unconditional logistic regression and adjusted for age and gender. A stepwise multiple linear regression analysis was employed to identify significant predictors of the number of drug doses taken per month. No significant association was found between 5HT2A A and 1438G and C516T gene polymorphisms and MOH risk. In contrast, a higher consumption of monthly drug doses was observed among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients (median 30, range 12-128) (Mann-Whitney U-test, P = .018). In the stepwise multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of overused drug (P = .047) emerged as significant, independent predictors of the monthly drug consumption in MOH patients. Although our results do not support a major role of the A-1438G and C516T polymorphic variants of the 5HT2A gene in the susceptibility of MOH, our findings support an influence of the C516T polymorphism on the number of symptomatic drug doses taken and, possibly, on the drug-seeking behavior in these patients.

Interaction between serotonin 5-HT2A receptor gene and dopamine transporter (DAT1) gene polymorphisms influences personality trait of persistence in Austrian Caucasians

We examined 89 normal volunteers using Cloninger's Temperament and Character Inventory (TCI). Genotyping the 102T/C polymorphism of the serotonin 5HT2A receptor gene and the ser9gly polymorphism in exon 1 of the dopamine D3 receptor (DRD3) gene was performed using PCR-RFLP, whereas the dopamine transporter (DAT1) gene variable number of tandem repeats (VNTR) polymorphism was investigated using PCR amplification followed by electrophoresis in an 8% acrylamide gel with a set of size markers. We found a nominally significant association between gender and harm avoidance (P=0.017; women showing higher scores). There was no association of either DAT1, DRD3 or 5HT2A alleles or genotypes with any dimension of the TCI applying Kruskal–Wallis rank-sum tests. Comparing homozygote and heterozygote DAT1 genotypes, we found higher novelty seeking scores in homozygotes (P=0.054). We further found a nominally significant interaction between DAT1 and 5HT2A homo-/heterozygous gene variants (P=0.0071; DAT1 and 5HT2A genotypes P value of 0.05), performing multivariate analysis of variance (MANOVA). Examining the temperamental TCI subscales, this interaction was associated with persistence (genotypes: P=0.004; homo-/heterozygous gene variants: P=0.0004). We conclude that an interaction between DAT1 and 5HT2A genes might influence the temperamental personality trait persistence.

Association Between T102C Polymorphism of Serotonin 2A Receptor Gene and Urinary Incontinence in Older Women

BackgroundThe bladder's regulatory function is influenced by central serotonergic modulation. T102C polymorphism of the serotonin 2A (5-HT2A) receptor gene is associated with urinary incontinence (UI) that has been reported by...