Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats

Recent studies have reported a genetic association between the -1438 G/A polymorphism within the promoter region of the 5-HT(2A) receptor gene and eating disorders (ED), with conflicting results. To clarify the role of the -1438 G/A polymorphism in different ED categories we have analyzed the genotype and allele frequency distribution in 54 Italian patients with Binge ED (BED) compared to 132 obese non-BED subjects. No significant differences were found between obese BED and obese non-BED individuals, suggesting that this polymorphism does not genetically distinguish these two phenotypes. Moreover, the evaluation of 148 patients with anorexia nervosa and 86 patients with bulimia nervosa revealed an association of the A allele with both these disorders.     

The serotonin 2A -1438 G/A receptor polymorphism in a group of Swedish male criminals

Studies have shown that genetic components to some extent underlie behavioral disorders such as impulsive aggression and violence, and that central serotonergic mechanisms are involved in the development of such behavior. In the present study, we analyzed a polymorphism in the gene encoding the serotonin 2A receptor (5-HT2A -1438 G/A) in a group of Swedish criminals (n=97) and in a group of healthy Swedish blood donors (n=202). The 5-HT2A -1438 GG genotype was lower in the criminal group than in the control group (P=0.034). In accordance with previous results, no associations were found between the 5-HT2A -1438 G/A polymorphism and personality as measured by Karolinska Scales of Personality. Neither were there any associations between the studied polymorphism and the type of crime committed.     

5-HTR2A基因启动子区-1438G/A多态性与抗精神病药源性肥胖的核心家系关联研究

目的探讨中国汉族首发精神分裂症(schizophrenia,SCH)患者抗精神病药物(antipsychoticagents,APS)治疗过程中体重增加是否与五羟色胺2A受体(5-hydroxytryptamine2Areceptor,5-HTR2A)基因启动区-1438G/A多态性相关。方法对84例首发精神分裂症患者(包含完整核心家系70个)APS(氯丙嗪或利培酮)单药治疗10周,治疗前后测量体重并计算体重指数。采用聚合酶链反应-限制性片段长度多态技术分析5-HTR2A基因启动区-1438G/A多态性基因型和等位基因分布频率,进行APS所致体重增加与5-HTR2A基因启动区-1438G/A多态性的相关分析、传递不平衡检验及数量性状传递不平衡检验。结果治疗10周后患者体重较基础体重增加(8.00±6.13)%。APS治疗10周后,体重增加≥7%和<7%患者组间,5-HTR2A基因-1438G/A多态性各基因型和等位基因分布频率差异均无统计学意义(P>0.05)。5-HTR2A基因-1438G/A多态性的各基因型之间各项指标的差异均无统计学意义(P>0.05);同时未发现5-HTR2A基因-1438G/A在不同体重增加组间存在传递不平衡。结论5-HTR2A基因-1438G/A多态性可能不是影响APS所致体重增加的主要遗传因素。     

Seasonality associated with the serotonin 2A receptor -1438 A/G polymorphism

BACKGROUND: Seasonal affective disorder and seasonal rhythms in mood and behavior (seasonality) have been reported to be associated with serotonergic system. In this study we investigated the relationship between the serotonin 2A receptor (5HTR2A) -1438 A/G polymorphism and seasonal variation in a young Korean healthy population. METHODS: 297 young Korean medical students were recruited for this study. They were genotyped for the 5HTR2A -1438 A/G polymorphism and evaluated the seasonal variation in mood and behavior by the Seasonality Pattern Assessment Questionnaire (SPAQ). RESULTS: The Global Seasonality Score of the SPAQ among three genotypes were not different. However, the comparison between seasonals and non-seasonals showed significant difference in the genotype distribution. The winter-type seasonals showed a significantly higher frequency of the 5HTR2A -1438 A allele compared with non-seasonals (chi2 = 6.80, p = 0.009; OR = 1.79; 95% CI, 1.15-2.78). CONCLUSION: These results suggest that the 5HTR2A -1438 A/G polymorphism is possibly related to seasonality in the Korean population.     

Increased nitric oxide production in eating disorders

Animal studies showed that nitric oxide (NO)/cyclic-GMP (cGMP) pathway is involved in the modulation of eating behavior. To address its role in eating disorders (ED), plasma nitrite and cGMP levels were studied in 50 ED patients (25 with Anorexia Nervosa, AN; 25 with Bulimia Nervosa, BN) and 20 sex- and age-matched controls (C). Nitrites (nmol/mg protein, mean+/-S.E.M.: any ED 1.01+/-0.29; AN 1.15+/-0.47; BN 0.88+/-0.36; C 0.25+/-0.07; p<0.01) and cGMP (nmol/ml plasma, mean+/-S.E.M.: any ED 2.58+/-0.60; AN 2.81+/-1.10; BN 2.41+/-0.70; C 0.11+/-0.05; p<0.01) were significantly higher in ED patients than in C. Nitrite and cGMP levels inversely correlated with BMI in AN patients (nitrites: r=-0.62 p<0.01; cGMP r=-0.45 p<0.05) but not in BN patients (nitrites: r=-0.15 p=0.49; cGMP: r=-0.05 p=0.13) or in control subjects (nitrites: r=0.11 p=0.98; cGMP r=0.37 p=0.32). Significant correlations were also present in bulimic patients between nitrite levels, frequency of binges and several psychopathological dimensions, as assessed through the EDE. This is the first evidence of an alteration of the NO pathway in ED patients. Further studies are needed to ascertain whether an increase in NO levels plays a possible role in the pathogenesis of ED.     

Contribution of 5-HT2A receptor gene -1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents.

Attention-deficit/hyperactivity disorder (ADHD) typically emerges before 7 years of age and may persist into adolescence or adulthood. The adolescent outcome can be classified into four types, including non-remission, syndromatic remission, symptomatic remission, and functional remission. Genetic factors are believed to contribute to symptom stability and change across development, so adolescent outcome may be a sub-phenotype for molecular genetic studies of ADHD. Serotonin system genes are prime candidates for this sub-phenotype, since the development of this neurotransmitter system parallels the course of ADHD. The current study examined the association between adolescent outcome in ADHD and serotonin system genes, including the -1438A>G polymorphism of the serotonin 2A receptor gene (HTR2A) and the -759C>T polymorphism of the serotonin 2C receptor gene (HTR2C). The -1438A>G polymorphism was found to be related to remission in ADHD, especially functional remission (P = 0.029). Due to potential phenotypic and etiologic heterogeneity in ADHD, the results of this study must be replicated in additional samples before they can be generalized to other populations.     

The serotonin-2A receptor polymorphism and smoking behavior in Japan

Epidemiological and genetic studies on smoking behavior have been performed, and in this study the human serotonin 2A receptor (HTR2A) polymorphism was examined in 82 smoking behaviorists and 125 healthy controls. HTR2A consists of at least 14 subtypes, depression and anxiety occur due to agonists, and hallucination, fever heat, psychomotor excitement and other symptoms also occur. The polymorphism in HTR2A (102T/C, -1438A/G) was identified by means of the polymerase chain reaction followed by restriction fragment length polymorphism, and the Fagerstrom Test for Nicotine Dependence was used to determine the extent of smoking behavior. The results suggest that the HTR2A (102T/C, -1438G/A) polymorphism might not be associated with susceptibility to a risk factor for developing smoking behavior. Further studies are required to determine whether or not the novel serotonin receptor (5-HTR) polymorphism reflects the pathogenesis of smoking behavior.     

Negative symptoms of schizophrenia could explain discrepant data on the association between the 5-HT2A receptor gene and response to antipsychotics

Pharmacogenetic studies assessing the role of 5-HT(2A) receptor gene in antipsychotic efficacy yielded conflicting data. Phenotypical heterogeneity of schizophrenia might explain such discrepancies. For example, negative symptoms are known to reflect severity of illness and to restrain therapeutic response. On this basis, we re-assessed the possible influence of the -1438A/G polymorphism of the 5-HT(2A) receptor gene on the clinical efficacy of atypical antipsychotics with focus on several relevant dimensions. One hundred and sixteen French schizophrenic subjects treated for at least 1 month by atypical antipsychotics were screened for treatment response according to the May and Dencker scale. Gender, age at onset, duration and severity of illness, intensity of negative and positive symptoms at discharge were investigated. The intensity of negative symptoms at discharge was the only variable explaining May and Dencker score (p < 0.001), and was significantly associated with the AA genotype of the -1438A/G polymorphism of the 5-HT(2A) receptor gene (p = 0.03). However, the A allele was not independently associated with refractoriness to atypical antipsychotics. Accordingly, the score reached in the Scale for the Assessment of Negative Symptoms (SANS) appeared as a confounding factor between therapeutic response and the -1438A/G polymorphism of the 5-HT(2A) receptor gene, at least in our sample. This data indicate that negative symptoms are worth being systematically assessed in pharmacogenetic studies aimed at analysing candidate genes in schizophrenia.     

Serotonin 2A receptor gene polymorphism and personality traits: no evidence for significant association

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n = 239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits.     

The -1438A/G polymorphism in the 5-hydroxytryptamine receptor 2A gene is related to hyperuricemia, increased gamma-glutamyl transpeptidase and decreased high-density lipoprotein cholesterol level in the Japanese population: a prospective cohort study over 5 years

This prospective cohort study in Japanese workers examined the relationship between the -1438A/G polymorphism in the 5-hydroxytryptamine receptor 2A gene and the development of positive findings for various life-style-related disorders. This study over the 5-year period, 1997-2002, included observations of several disorders in cohorts ranging between 560-1023 for males and 477-735 for females who had negative findings for each disorder at baseline. The criteria for development of the disorders were: hypertension, systolic blood pressure > or =140 mmHg or dia-stolic blood pressure > or =90 mmHg or taking antihypertensive medication; overweight, body mass index (BMI) > or =25 kg/m(2); obesity, BMI > or =30 kg/m(2); new onset of cerebral stroke; metabolic abnormalities, glycosylated hemoglobin A1c >6.0%, total cholesterol > or =240 mg/dl, high-density lipoprotein cholesterol <40 mg/dl, uric acid >7.0 mg/dl, gamma-glutamyl transpeptidase > or =60 IU/l in males and > or =30 IU/l in females. Pooled logistic regression analyses were performed using the -1438A/G genotype and other potential factors as covariates. The odds ratios to AA genotype were significant for uric acid (GG, 0.52; AG, 0.59), obesity (AG, 0.24) in males and for high-density lipoprotein cholesterol (GG, 0.11; AG, 0.36), gamma-glutamyl transpeptidase (GG, 0.53; AG, 0.62) and total cholesterol (GG, 1.84) in females. The present study is the first prospective cohort investigation to demonstrate that the -1438G allele has a protective effect against the development of a range of cardiovascular and metabolic disorders. This study indicates that the -1438A/G polymorphism is an independent factor for various disorders in the general Japanese population and suggests that targeting of this polymorphism may be beneficial for preventing these disorders in Japan.     

Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects

Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA(A)gamma2, and the serotonin transporter (5-HTT) were analyzed for association with heroin abuse. We examined three polymorphisms (promoter - 141DeltaC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter - 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABA(A)gamma2 gene in 121 Chinese heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism - 141DeltaC (genotype-wise and allele-wise, P = 0.05, uncorrected). An additional 344 subjects with heroin abuse and 104 controls were investigated for the - 141DeltaC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with heroin abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of heroin and controls (genotype-wise, P = 0.006, allele-wise, P = 0.016) but not for injectors of heroin (genotype-wise, P = 0.81, allele-wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with heroin abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABA(A)gamma2 genes are not likely to be a major genetic risk factor for heroin abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter - 141DeltaC polymorphism.     

自杀未遂与5-羟色胺2A受体基因的关联分析

目的 探讨5-羟色胺（5-HT）2A受体基因A-1438G和T102C两种多态性与自杀未遂之间的关系。方法 以149例自杀未遂者为研究对象。190名正常人为对照,采用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法,分析5-HT2A受体基因A-1438G和T102C多态性。结果 PCR-RFLP分析发现,男性自杀未遂与5-HT2A受体基因A-1438G多态性的基因型GG关联。结论 5-HT2A受体基因A-1438G多态性可能与男性的自杀易感性相关。     

Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility

Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI=2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR=4.0, CI=2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI=0.3-6.3, P=0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI=1.3-3.1, P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR=2.1, CI=1.6-2.7, P<0.001), but not in Asian (OR=1.4, CI=0.8-2.3, P=0.2) or African (OR=1.2, CI=0.6-2.5, P=0.59) populations. In summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.     

Mental representations of attachment in Eating Disorders: a pilot study using the Adult Attachment Interview

Mental representations of attachment in a sample of adults with Eating Disorders (ED) were assessed using the Adult Attachment Interview (AAI). Sixty subjects participated in the study: 30 non-clinical and 30 clinical. The results obtained showed a specific distribution of attachment patterns in the clinical sample: 10% Free/Autonomous (F), 47% Insecure-Dismissing (Ds), 17% Insecure-Entangled/Preoccupied (E) and about 26% disorganized (CC/U). The two samples differed in their attachment pattern distribution and were significantly different on some coding system scales. Further information was obtained by analyzing differences between the three ED subtypes considered (i.e. Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorder) and by investigating the differential role of the two parental figures in the definition of attachment representations. Results showed potential benefits in using the AAI coding system scales in addition to the main classifications in order to understand better the developmental issues involved in these disorders. Implications for developmental research and clinical nosology are discussed.     

Association between the Interleukin 10-1082G>A polymorphism and coronary heart disease risk in a Caucasian population: a meta-analysis

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and studies have shown the involvement of IL-10 in the atherosclerotic process. The IL-10-1082G/A polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with coronary heart disease (CHD) risks, but previous results have been conflicting. We performed a meta-analysis using six eligible case-control studies (including 14 data sets) with a total of 5006 patients and 3968 controls to summarize the existing data on the association between the IL-10-1082G/A polymorphism and CHD risk. Compared with the common IL-10-1082G/A GG genotype, the carriers of variant genotypes (IL-10-1082GA/AA) had a 1.12-fold elevated risk of CHD (95% CI = 1.01-1.23, P = 0.03) under the dominant genetic model, as estimated using a random effect model. The effect of the IL-10-1082G/A polymorphism was further evaluated using stratification analysis. In the three disease of artery studies, with the variant genotypes had a not obvious increased risk of disease of artery (OR = 1.19, 95% CI = 0.98-1.44, P = 0.08) as estimated using a fixed effect model. Similar results were found in the nine myocardial infarction studies (OR = 1.13, 95% CI = 1.00-1.27, P = 0.05). It was also demonstrated that the increased risk of CHD associated with IL-10-1082G/A variant genotypes was more pronounced in Caucasians (OR = 1.12, 95% CI = 1.01-1.23, P = 0.03). Our meta-analysis suggests that the IL-10-1082G/A polymorphism genotypes (GA+AA) might be associated with an increased risk of CHD, especially in Caucasians.     

Cultural consonance,a 5HT2A receptor polymorphism,and depressive symptoms: A longitudinal study of gene × culture interaction in urban Brazil

In this study in urban Brazil we examine, as a predictor of depressive symptoms, the interaction between a single nucleotide polymorphism in the 2A receptor in the serotonin system (?1438G/A) and cultural consonance in family life, a measure of the degree to which an individual perceives her family as corresponding to a widely shared cultural model of the prototypical family. A community sample of 144 adults was followed over a 2‐year‐period. Cultural consonance in family life was assessed by linking individuals' perceptions of their own families with a shared cultural model of the family derived from cultural consensus analysis. The ?1438G/A polymorphism in the 2A serotonin receptor was genotyped using a standard protocol for DNA extracted from leukocytes. Covariates included age, sex, socioeconomic status, and stressful life events. Cultural consonance in family life was prospectively associated with depressive symptoms. In addition, the interaction between genotype and cultural consonance in family life was significant. For individuals with the A/A variant of the ?1438G/A polymorphism of the 2A receptor gene, the effect of cultural consonance in family life on depressive symptoms over a 2‐year‐period was larger (β = ?0.533, P < 0.01) than those effects for individuals with either the G/A (β = ?0.280, P < 0.10) or G/G (β = ?0.272, P < 0.05) variants. These results are consistent with a process in which genotype moderates the effects of culturally meaningful social experience on depressive symptoms. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Association of the promoter polymorphism -1438G/A of the 5-HT2A receptor gene with behavioral impulsiveness and serotonin function in women with bulimia nervosa.

Separate lines of research suggest that the functional alterations in the serotonin (5-HT) 2A receptor are associated with 5-HT tone, behavioral impulsiveness, and bulimia nervosa (BN). We explored the effect of allelic variations within the 5-HT2A receptor gene promoter polymorphism -1438G/A on trait impulsiveness and serotonin function in women with BN. Participants included women with BN having the A allele (i.e., AA homozygotes and AG heterozygotes, BNA+, N = 21); women with BN but without the A allele (i.e., GG homozygotes, BNGG, N = 12), and normal eater control women having the A allele (NEA+, N = 19) or without the A allele (NEGG; N = 9). The women were assessed for psychopathological tendencies and eating disorder symptoms, and provided blood samples for measurement of serial prolactin responses following oral administration of the post-synaptic partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). The BNGG group had higher scores than the other groups on self-report measures of non-planning and overall impulsiveness and had blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other Axis I mental disorders. Findings indicate that women with BN who are GG homozygotes on the -1438G/A promoter polymorphism are characterized by increased impulsiveness and lower sensitivity to post-synaptic serotonin activation. These findings implicate the GG genotype in the co-aggregation of impulsive behaviors and alterations of post-synaptic 5-HT functioning in women with BN.     

Association of MIF-173G/C and MBL2 codon 54 gene polymorphisms with rheumatoid arthritis: A meta-analysis

The aim of this study was to evaluate the association between macrophage migration inhibitory factor (MIF) -173G/C (rs755622), mannose-binding lectin (MBL2) exon 1 codon 54 (rs1800450) gene polymorphisms and rheumatoid arthritis (RA) susceptibility in ethnically different populations. A meta-analysis was conducted (allelic contrast, the additive model, the dominant model and the recessive model) on the MIF-173G/C polymorphism across five studies (four European and one Asian studies), and the MBL2 codon 54 polymorphism with five studies (four Asian and one European studies), respectively. Meta-analysis indicated an association between the MIF-173G/C in all study subjects in allelic contrast (OR=1.19, 95%CI: 1.05-1.35, P=0.001), the additive model (OR=1.68, 95CI: 1.13-2.49, P=0.001), the dominant model (OR=1.17, 95CI: 1.01-1.35, P=0.003), the recessive model (OR=1.63, 95CI: 1.10-2.42, P=0.001). While stratified by ethnicity with European populations, an association was found in allelic contrast (OR=1.20, 95CI: 1.04-1.38, P=0.002), the additive model (OR=1.85, 95CI: 1.19-2.88, P=0.001), the dominant model (OR=1.20, 95CI: 1.02-1.41, P=0.003). With respect to MBL2 codon 54 polymorphism and RA, no association was found in all study subjects in all comparisons, but there was an association while stratified by ethnicity with Asian populations in the dominant model (OR=1.50, 95CI: 1.01-2.23, P=0.007). In conclusion, the present study suggests that the MIF-173G/C polymorphism is associated with RA susceptibility, but the MBL2 codon 54 polymorphism is not associated with RA.     

Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors, which make genes from the serotonin system reasonable candidates for ADHD susceptibility. In the present study, we investigated a polymorphism in the promoter region of the serotonin transporter (SLC6A4) and two polymorphisms (-1438 A > G and His452Tyr) in the serotonin 5-HTR2A receptor gene using family based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No linkage disequilibrium between the two HTR2A polymorphisms was detected in this sample (P = 0.76). Considering several evidences from animal models for sexual dimorphism in serotonin genes expression, analyses were performed separately for the whole sample and for male probands. No evidences for biased transmissions of both HTR2A -1438 A > G and SLC6A4 polymorphisms to ADHD youths were observed. Preferential transmission of the HTR2A His452 allele was observed only in families with affected boys (P = 0.04). Our results suggest that findings from ADHD association studies for serotonin genes might be understood in the context of a gender effect, which may help to explain conflicting results in these association studies.     

海洛因依赖与儿茶酚胺氧位甲基转移酶基因-287A/G多态性的关联研究

目的 探讨海洛因依赖和儿茶酚胺氧位甲基转移酶（catechol-O-methyltransferase,COMT)ADLD－287A/G多态性的关系。方法 采用PCR技术，检测了268例海洛因依赖者和177名正常对照的COMT基因－287A／G多态性。结果 海洛因依赖者COMT基因－287A／G多态的基因型AA的频率显著高于对照组9x^2=7.41,=0.025)，等位基因A的频率也显著高于对照组（X^2=5.69,P=0.017)。结论提示COMT基因－287A／G多态性与海洛因依赖的易感性有关。