Polymorphism of the serotonin 2A receptor gene (5HTR2A) and personality traits

The interindividual variation of temperament features (such as anxiety, neuroticism, harm avoidance) is determined, in particular, by allele polymorphism of genes involved in serotonin metabolism and has earlier been associated with the insertion/deletion polymorphism of the serotonin transporter gene. Polymorphic alleles of the serotonin 2A receptor gene (5HTR2A) were tested for association with personality traits assessed with several tests. The T102C and A1438G polymorphisms were associated with a variation in emotionality, activity, and sociability, which are integral characteristics of temperament. With each polymorphism, differences were significant only between heterozygotes and homozygotes. Carriers of T102C genotype A1/A2 displayed a lower level of anxiety-related traits, a higher score on scale Hypomania, and a lower score on scale Social Introversion and were assumed to have higher activity and sociability. Carriers of A1428G genotype A/G differed from homozygotes G/G in having a lower level of social introversion and a lower score on scale No close friends, which testified to higher sociability of heterozygotes. Thus, the polymorphic alleles of SHTR2A proved to be associated with personality traits in mentally healthy people.     

Serotoninergic polymorphisms (5-HTTLPR and 5-HT2A): association studies with psychosis in Alzheimer disease

Patients with Alzheimer disease (AD) often exhibit psychotic symptoms associated with cognitive impairment. A few association studies have been carried out to determine if the serotonin transporter and receptor genes are potential risk factors for AD and/or associated psychopathology. The aim of this study was to investigate the association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with the risk of developing dementia and/or psychotic symptoms in a group of sporadic AD patients from Italy. No significant differences in the distribution of allele and genotype frequencies of 5-HTTLPR and 5-HT2A T102C were found between patient and control groups. However, a significant association between the C102/C102 5-HT2A genotype and psychotic symptoms (p < 0.001) was observed. Our data strongly confirm results from previous studies suggesting that the C102 allele of the 5-HT2A receptor is associated with the occurrence of psychotic symptoms in AD. On the contrary, the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of the disease.     

Polymorphism of the Serotonin 2A Receptor Gene (5HTR2A) and Personality Traits

The individual variation of temperament features (such as anxiety, neuroticism, harm avoidance) is determined, among other things, by allele polymorphism of genes involved in serotonin metabolism and has earlier been associated with the insertion/deletion polymorphism of the serotonin transporter gene. Polymorphic alleles of the serotonin 2A receptor gene (5HTR2A) were tested for association with personality traits assessed in several tests. The T102C and A1438G polymorphisms were associated with variation in emotionality, activity, and sociability, which are integral characteristics of temperament. With each polymorphism, differences were significant only between heterozygotes and homozygotes. Carriers of T102C genotype A1/A2 displayed a lower level of anxiety-related traits, a higher score on the Hypomania scale, and a lower score on the Social Introversion scale and were assumed to have higher activity and sociability. Carriers of A1438G genotype A/G differed from homozygotes G/G in having a lower level of social introversion and a lower score on the No Close Friends scale, which testified to higher sociability of heterozygotes. Thus, the polymorphic alleles of 5HTR2A proved to be associated with personality traits in mentally healthy people.     

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity

Background

Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP) is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs) in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.

Methods

A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ) and hospital anxiety and depression scale (HADS). Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT) were analyzed in healthy subjects.

Results

There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.

Conclusions

Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.     

Does genetic background moderate the association between parental education and school achievement?

This study was conducted with a purpose to examine whether the T102C polymorphism of the serotonin receptor 2A (HTR2A) gene moderates the association between parental education and children's school achievement across nine compulsory school years. The study was carried out in a population‐based sample of Finnish students (aged 9, 12 and 15 years, n = 982). It was found that the HTR2A gene was not related to the school achievement at any school level, but moderated the association between maternal education and the children's grade point averages. The T/T genotype carriers benefited most from high‐maternal education, and suffered from a low one more than the carriers of the other variants of the HTR2A gene. The present finding may at least partly answer the important question why academic outcomes of environmental interventions vary even at the same intelligence levels of the students.     

Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population

The aim of this study was to investigate the possible association of serotonin 2A receptor gene (HTR2A) -1438 G/A polymorphism and CYP1A2 gene 163C/A polymorphism with tardive dyskinesia (TD) in a Turkish population. A total of 47 patients with persistent TD, 80 patients who were consistently without TD, and 100 healthy controls were included in this study. The polymorphic regions of -1438 G/A polymorphism of HTR2A receptor gene (rs6311) and 163C/A of CYP1A2 (rs762551) gene were amplified using polymerase chain reaction (PCR), followed by digestion with restriction enzymes MspI and Bsp1201. Genotype and allele frequencies were calculated by the chi(2)-test. Crude and adjusted odds ratios (ORs) were estimated, and 95% confidence intervals (CIs) were computed by multivariate logistic regression analysis. The genotype and allele frequencies of HTR2A and CYP1A2 gene were similar in schizophrenia with TD, schizophrenia without TD, and healthy controls. The logistic regression analysis showed that cumulative exposure to antipsychotic drugs for every year (p = 0.003; OR = 1.15; CI = 1.07-1.23), and AA genotype of HTR2A gene (p = 0.0258; OR = 4.34; CI = 1.19-15.81) are risk factors for TD. The same logistic regression model showed no association between CYP1A2 polymorphism and TD. The results of the present study seem to indicate that HTR2A gene polymorphism influences the tendency to express TD following prolonged antipsychotic drug exposure in Turkish schizophrenia patients.     

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.     

5-羟色胺受体基因多态性位点与海洛因依赖的关联性研究

目的：5-HT（5-hydroxytryptamine,5-HT）参与了多种中枢神经活动的生理过程,其功能异常可以影响很多行为障碍,已有研究显示,5-HT水平与多种精神疾病密切相关。5-HT受体及其转运体基因在海洛因依赖发生发展中起到了重要的作用,是海洛因依赖的主要候选基因。探讨5羟色胺2A受体（Serotonin 2A receptor,HTR2A）基因启动子区-1438A/G（rs6311）、外显子区102T/C（rs6313）与5羟色胺1B受体（Serotonin 1B receptor,HTR1B）基因外显子区861G/C（rs6296）3个单核苷酸多态性和海洛因依赖的关联性分析。方法：严格按照诊断标准,选取无亲缘关系的海洛因依赖个体616例及健康个体600例提取基因组DNA,采用PCR-RFLP方法检测rs6311、rs6313和rs6296 3个SNPs位点的基因型频率,采用SPSS16.0软件分析各位点等位基因、基因型频率在病例-对照组间差异。结果：HTR2A基因rs6311和HTR1B基因rs6296位点的等位基因及基因型频率分布在2组间存在统计学差异（P〈0.05）,病例组rs6311位点的等位基因A频率显著高于对照组（X2=5.436,P=0.020,OR=1.208,CI=1.031~1.417）,rs6296位点的等位基因C频率显著高于对照组（X2=12.116,P=0.000,OR=1.329,CI=1.132~1.560）。连锁不平衡检验结果显示,HTR2A基因rs6311、rs6313位点处于不连锁状态,D＇〈0.5。结论：HTR2A基因rs6311和HTR1B基因rs6296多态性可能与海洛因成瘾有关,携带有rs6311 A等位基因与rs6296 C等位基因的人可能更容易对海洛因产生依赖。我们的研究为海洛因依赖易感人群筛选及药物靶向治疗提供了理论依据。     

上海地区汉族人5-HT2a受体基因T102C多态性的基因频率分布

为了揭示中国汉族人5-HT2a受体基因T102C多态性基因频率的分布,我们随机抽取了226例汉族健康人作研究,用限制性片段长度多态性(RFLPs)技术测定研究对象的基因型和等位基因。结果发现汉族正常人5-HT2a受体基因T102C多态性基因型频率依次为:A1/A2=0.5044,A1/A1=0.2965,A2/A2 =0.1991,两种等位基因频率依次为:A1=0.5487,A2=0.4513,杂合度H=0.50 44、期望杂合度h=0.4953,多态信息量PIC=0.3726,表明T102C多态性具有合适信息,对疾病的关联研究,法医学鉴定有一定的价值。 Abstract:To investigate the distribution about genotype and allele frequencies of T102C polymorphism in the 5-HT2a receptor gene Chinese Han population,the genotypes and alleles of 226 healthy person were examined with Restriction Fragment Length Polymorphisms(RFLPs)technique.The genotype frequencies are as follows:A1/A2=0.5044,A1/A1=0.2965,A2/A2=0.1991,respectively,and the allele frequencies are as follows:A1=0.5487,A2=0.4513,respectively.The heterozygosity(H)is 0.5044,the expected heterozygosity(h)is 0.4953,and the Polymorphism Information Content(PIC)is 0.3726.Our findings suggest that the T102C polymorphism in 5-HT2a receptor gene may have suitable information to be used for association study or forensic identification.     

中国人群5—羟色胺2A受体基因中T102C多态性与精神分裂症的联系

在研究５－羟色胺２Ａ受体基因多态性与精神分裂症的关联分析中,调查了２０２例精神分裂症患者及２０２例正常对照。各相匹配组间比较未发现基因型和等位基因频率的显著性差异。结果提示,在中国人群中５－羟色胺２Ａ受体的静态Ｔ１０２Ｃ突变与精神分裂症之间不存在关联。     

No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia

The A(-1438)G promoter polymorphism of the 5-hydroxytryptamine 2a receptor (5-HT2AR) gene and its influence on the cortical density of 5-HT2AR was studied using brain tissue donated at autopsy from 58 schizophrenic and 64 non-schizophrenic subjects. A linkage between genotypes for the A(-1438)G and a T102C polymorphic site identified in a previous study was observed. Our data suggest no association of the A(-1438)G polymorphism with schizophrenia and no effect of the promoter genotype upon 5-HT2AR densities in either the schizophrenic or non-schizophrenic groups.     

Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren

The purpose of this study was to assess the influence of single nucleotide polymorphism 3 (SNP3) of the apolipoprotein A-V ( APOA5) gene on the serum triglyceride (TG) level in Japanese schoolchildren. To determine the frequency of the genotype, we analyzed 552 schoolchildren. The frequencies of the T/T, T/C and C/C genotypes of the APOA5 gene were 225 (40.8%), 263 (47.6%) and 64 (11.6%), respectively. The serum TG level was significantly different among the genotypic groups after adjustments for age, gender and obesity index (T/T 71.6+/-34.8 mg/dl, T/C 80.7+/-36.1 mg/dl, C/C 94.4+/-69.4 mg/dl, P<0.0001). The odds ratio (95% confidence interval) for hypertriglyceridemia of the C allele was 2.4 (1.0-6.2). Our data suggested that the T/C promoter region polymorphism of the APOA5 gene appears to be a genetic risk factor for hypertriglyceridemia in Japanese children.     

HTR2A基因多态性与云南彝族酒精依赖关联性研究

目的：探讨酒精依赖和云南彝族5-羟色胺2A受体（HTR2A）基因多态之间的关系。方法：采用PCR-RFLP技术对330健康人（对照组）和110名酒精依赖者（病例组）的5-HT2A受体基因的遗传多态性进行检测。结果：在440例样本中共检测到2种等位基因A和G,三种基因型AA,AG,GG．三种基因型在对照组中频率分别是38．5％,55．8％,5．8％;在病例组中的频率分别是30％,63．6％,6．4％。结论：在云彝族人群中,HTR2A基因rs6311（A－1438G）位点与酒精依赖无显著关联,HTR2A基因rs6311（A-1438G）位点在云南汉族和云南彝族酒精依赖组中无显著差异,但是在健康对照组中存在关联性．     

Relationship of beta(3)-adrenergic receptor polymorphism with metabolic syndrome and oxidative stress parameters in postmenopausal women

INTRODUCTION: Some studies indicate, that the Trp(64)/Arg(64) polymorphism of beta(3)-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of our study was evaluation of frequency of this ADRB3 polymorphism and his association with metabolic syndrome parameters and oxidative stress in postmenopausal women. MATERIAL AND METHODS: We performed the study among 94 women, aged 50-60, selected randomly from Wroclaw city population. Estimation of anthropometric parameters, densitometry (total body fat, android and gynoid deposits--using DPX(+) Lunar, USA device) and biochemical estimations such as lipid profile, glucose, insulin, estradiol and FSH serum level (using commercial kits) were carried out. Oxidative stress was estimated by measurement of thiobarbituric-reactive substances (TBARS) serum concentration, using Yagi method, on spectrofluorimeter Perkin-Elmer LS55. Blood for analysis was collected before, direct after and 6 h after the 30-minutes physical test using cycloergometer. ADRB3 genotyping was performed by PCR and mini-sequencing using ABI 310 sequencer (Applied Biosystems). RESULTS: The frequency of Trp(64)/Arg(64) genotype in investigated population was 15.8%. The Arg(64)/Arg(64) genotype had only one woman. Women bearing Trp(64)/Arg(64) genotype showed higher mean serum level of triglycerides and lower serum level of HDL-cholesterol in comparison to women bearing Trp(64)/Trp(64) genotype, however without statistical significance (p > 0.05) (respectively, means +/- SD for triglycerides: 140.3 +/- 64.1 vs. 113.9 +/- 56.2 mg/dl; and for HDL-cholesterol: 60.9 +/- 11.9 vs. 67.0 +/- 16.9 mg/dl). Both groups did not differ in any other investigated anthropometric nor biochemical parameter. CONCLUSIONS: 1. The Trp(64)/Arg(64) polymorphism of beta(3)-adrenergic receptor could be associated with lipid profile disorders observed in metabolic syndrome in postmenopausal women, however it should be explained basing on the study with more included subjects. 2. The Trp(64)/Arg(64 )polymorphism of beta(3)-adrenergic receptor has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women.     

Polymorphism of the serotonin receptor (5-HTR2A) gene and verbal fluency in normalcy and schizophrenia

To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the vocabulary), the T102C polymorphism of the serotonin receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or schizotypic disorders and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (N = 67), with homozygotes A2A2 having lower verbal fluency. The results did not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.     

血小板膜P2Y12受体基因T744C多态性对外伤性脑梗死(PTCI)患者血小板聚合率及疗效的影响

目的:外伤性脑梗死(posttraumatic cerebral infarction,PTCI)是颅脑损伤的常见并发症之一,P2Y12受体介导血小板聚集是血栓形成的重要通路,与血小板聚集形成密切相关。本研究探讨外伤性脑梗死发生发展与血小板膜P2Y12受体基因T744C基因多态性的关系。方法:用聚合酶链反应(PCR)和限制性酶切片段长度多态性(RFLP)技术对186例外伤性脑梗死患者P2Y12受体基因T744C多态性进行分析。分别在治疗前和治疗后对所有颅脑外伤患者的伤情GCS评分,并按基因型分组对照分析结果。结果:血小板膜T744C血小板膜T744C基因型基因频率分别为TT基因型59.14%、TC型32.26%、CC型8.60%,T等位基因75.27%、C等位基因24.73%;其中TT基因型对奥扎格雷反应较敏感,GCS评分预后好;而CC型对奥扎格雷反应性低,预后差。结论:T744C基因多态性中CC基因型可能导致外伤性脑梗死临床及预后存在明显的个体差异,与其对抗血小板药物抵抗有关。T744C的C等位基因可能是脑梗死的遗传危险因素,开展相关遗传学风险研究,对于进一步缓解脑梗症状、改善预后具有重要意义。     

Polymorphism of the Serotonin Receptor Type 2A (5-HTR2A) Gene and Verbal Fluency in Normalcy and in Schizophrenia

To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the internal vocabulary), the T102C polymorphism of the serotonin receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or disorders of the schizophrenic spectrum and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (n = 67), with homozygotes A2A2 having lower verbal fluency. The results do not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.     

Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. METHODS AND RESULTS: Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. CONCLUSIONS: IL6 genotype is associated with HDL-C response to exercise training.     

Serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on adulthood social attachment

The ability to form and maintain attachment relations with other people is crucial for mental health and well-being. The origins of attachment behaviors are often assumed to be in early experiences with other people, especially with primary caregivers. Preliminary evidence suggests that serotonergic system may be involved in attachment behaviors. We examined whether the T102C variant of the serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on social attachment in adulthood. The participants were 1070 women and men from the Young Finns Study with 27-year follow-up and two measurement times for the outcomes (n = 1836 person observations). Mothers reported their relationship quality with their children (participants) in childhood or adolescence. Social attachment was assessed by participant's self-reports on two measures (reward dependence scale of the Temperament and Character Inventory and the Relationship Questionnaire). High childhood maternal nurturance predicted high reward dependence and low avoidant attachment in carriers of the T/T genotype but not in the T/C or C/C genotype groups, while low maternal nurturance was associated with low reward dependence and high avoidant attachment in T/T genotype carriers but not in C allele carriers. Our result suggests that T/T genotype carriers were more influenced by their childhood nurturing environment, than their C allele carrying counterparts, thus providing evidence for differential susceptibility to childhood nurturing environment associated with the HTR2A gene.     

Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene

Studies have shown that selective modulator of estrogen receptor raloxifene, exerts hypolipemic properties at least partially through estrogen receptor alpha activation. To test the hypothesis that polymorphisms of estrogen receptor alpha are associated with the influence of 6 months raloxifene treatment on serum lipids, two intronic (PvuII and XbaI), and one exonic polymorphism (P325P) were analyzed in 49 postmenopausal women, mean age 62.5+/-5.7 years. In all subjects, the total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were determined before and after 6 months of raloxifene treatment. We were unable to find any relationship between estrogen receptor alpha genotype and serum lipids at baseline. At the end of 6 months treatment with raloxifene, the mean decrease of total cholesterol and LDL cholesterol, independently of genotypes, was highly significant, but no influence on HDL and triglycerides concentrations was found. Neither the PvuII nor XbaI ESR1 gene polymorphisms were associated with the magnitude of lipid changes after 6 months treatment, whereas the subjects with non-CC genotype of P325P mutation had significantly lower total cholesterol and LDL cholesterol concentrations, and higher decline of total cholesterol (p<0.05). CONCLUSION: Our data suggest that exonic, but not intronic polymorphisms of estrogen receptor alpha gene might intensify the cholesterol lowering effect of raloxifene.