The association between catechol-O-methyl-transferase Val108/158Met polymorphism and suicide

One of the candidate genes for suicide is also a gene in the pathway for catecholamine degradation encoding an enzyme catechol-O-methyl-transferase (COMT). It harbors a common functional polymorphism, a G to A nucleotide transition resulting in amino acid substitution from valine (Val) to methionine (Met) at position 158 (COMT Val(108/158) Met; rs4680), that has been associated with psychiatric disorders characterized with an increased risk of suicidal behavior. We have performed the first study on Caucasian population examining the association between completed suicide and the COMT Val(108/158) Met polymorphism. The study population consisted of 356 suicide victims and 198 control subjects. Significant difference in COMT Val(108/158) Met variants' (genotypes, alleles and Val carriers) distribution was found only in male groups, between controls and suicide victims (P = 0.018, P = 0.031, P = 0.005), and between controls and violent suicide victims (P = 0.026, P = 0.042, P = 0.010). The r value from the standardized residuals showed that the Met/Met genotype (r = 2.03) in the control group contributed to these significant differences. In contrast to male subjects, no significant differences in the frequency of the COMT Val(108/158) Met variants were detected between female control and female suicide groups; however, the power of calculation (range 0.161-0.680) was below the desired 0.800. In addition, the logistic regression analysis confirmed these significant differences. In conclusion, our results showed the overpresentation of the Met/Met genotype in male control subjects compared with male suicide victims, suggesting that this genotype of the COMT Val(108/158) Met might be a protective factor against suicide.     

COMT rs4680 Met is not always the ‘smart allele’: Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese

Catechol‐O‐methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two‐back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = ?0.118, t = ?2.367, P = 0.019, and the left hippocampus: β = ?0.099, t = ?1.949, P = 0.052) and better WM performance (β = ?0.110, t = ?2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population‐specific genetic effects.     

No association of COMT (Val158Met) genotype with brain structure differences between men and women

We examined the effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism (rs4680), on brain structure in a subset (N = 82) of general population members of the Northern Finland 1966 Birth Cohort, selected through a randomization procedure, aged 33-35. Optimised voxel-based morphometry was used to produce grey matter maps from each subject's high resolution T1 weighted brain magnetic resonance images, which were subsequently entered into a general linear model with COMT genotype as defined by Met allele loading, gender and genotype by gender interaction as independent variables. Additional analyses were carried out on grey matter volumes within the dorsal lateral pre-frontal cortex (DLPFC) to examine effects on overall DLPFC volume and also using the DLPFC as a mask for voxelwise analyses, as this is an area previously reported as associated with Met allele loading. We failed to find any statistically significant association with grey matter volume and Met allele loading in the COMT gene or interaction affects between COMT and gender in either the whole brain voxel-wise analysis or in the area of the DLPFC.     

No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population

The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case–control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.     

偏执型精神分裂症与4个涉及多巴胺代谢的基因之间的关联分析

精神分裂症是由多基因相互作用导致的复杂疾病。对其易感基因,儿茶酚氧位甲基转移酶基因（COMT）的众多报道充满了矛盾。在对偏执型精神分裂症研究中,我们用多基因座关联分析法研究了4个涉及神经递质多巴胺代谢的基因之间的相互作用。分析结果支持如下假说：COMT-136-BclI对Val^108/158Met有调控作用。当前者的基因型是CC时,后者的易感等位基因型是Met（A）;而当前者的基因型是GG时,后者的易感等位基因型是Val（G）。这一新的假说可以解释此前单基因座分析对Val^108/158Met(COMT)的截然相反的报道,同时也显示了多基因座分析对复杂疾病研究的必要性。      

Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences,arousal regulation and sleep

Dopamine has been implicated in the regulation of sleep–wake states and the circadian rhythm. However, there is no consensus on the impact of two established dopaminergic gene variants: the catechol-O-methyltransferase Val158Met (COMT Val158Met; rs4680) and the dopamine D4 receptor Exon III variable-number-of-tandem-repeat polymorphism (DRD4 VNTR). Pursuing a multi-method approach, we examined their potential effects on circadian preferences, arousal regulation and sleep. Subjects underwent a 7-day actigraphy assessment (SenseWear Pro3), a 20-minute resting EEG (analyzed using VIGALL 2.0) and a body mass index (BMI) assessment. Further, they completed the Morningness–Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). The sample comprised 4625 subjects (19–82 years) genotyped for COMT Val158Met, and 689 elderly subjects (64–82 years) genotyped for DRD4 VNTR. The number of subjects varied across phenotypes. Power calculations revealed a minimum required phenotypic variance explained by genotype ranging between 0.5% and 1.5% for COMT Val158Met and between 3.3% and 6.0% for DRD4 VNTR. Analyses did not reveal significant genotype effects on MEQ, ESS, PSQI, BMI, actigraphy and EEG variables. Additionally, we found no compelling evidence in sex- and age-stratified subsamples. Few associations surpassed the threshold of nominal significance (p < .05), providing some indication for a link between DRD4 VNTR and daytime sleepiness. Taken together, in light of the statistical power obtained in the present study, our data particularly suggest no impact of the COMT Val158Met polymorphism on circadian preferences, arousal regulation and sleep. The suggestive link between DRD4 VNTR and daytime sleepiness, on the other hand, might be worth investigation in a sample enriched with younger adults.     

Catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase (COMT) Val158Met polymorphism and risk of osteoporotic fracture

Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT Val158Met polymorphism is associated with bone mineral density. The aim of this study was to investigate associations between COMT Val158Met and osteoporotic fractures in Chinese Han patients. Case-control study of 320 patients with osteoporotic fractures and 320 healthy controls were conducted. The COMT Val158Met polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. Patients with osteoporotic fracture had a significantly lower frequency of Val/Val genotype [odds ratio (OR) = 0.62, 95% confidence interval (CI) 0.39–0.99, P = 0.04] than controls. When stratified by the fracture type, there was a significantly lower frequency of Val/Val genotype in patients with vertebral fracture (OR = 0.58, 95% CI 0.36–0.94, P = 0.03) than controls. There was no significant difference in the distribution of each genotype between patients with hip fracture and the control group. Our findings suggest that COMT Val/Val genotype was associated with a lower risk of osteoporotic fracture in Chinese population, especially to vertebral fracture.     

Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia

A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment and in various dementias. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (VAT) duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly lower scores of MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.     

COMT Val158Met and cognition: main effects and interaction with educational attainment

Studies in children have shown that the genetic influence on cognition is positively correlated with socioeconomic status. Catechol- O -methyltransferase (COMT) Val158Met, a common, functional polymorphism, has been implicated in executive cognition and working memory. Imaging studies have shown that the variant Met allele is associated with more efficient prefrontal cortical processing and better attention but also emotional vulnerability to stress. We hypothesized that COMT Val158Met genotype would interact with years of education (yrs ed), one indicator of socioeconomic adversity, to predict cognitive task performance. We therefore administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to 328 community-derived, genotyped, Plains American Indians (mean yrs ed = 12; range = 5–18). We found significant genotypic effects on WAIS-R measures of long-term memory, working memory and attention. The Met allele was associated with improved performance in the Information and Picture Completion subscales; Met/Met homozygotes performed the best. COMT genotype interacted with yrs ed to influence Information and Block Design scores: Met allele carriers' scores improved markedly with increasing yrs ed, whereas the scores of Val/Val individuals were only marginally influenced by yrs ed. There was a crossover of effects at 11–12 yrs ed: in the less educated group, Met allele carriers actually performed worse than Val/Val individuals perhaps because of emotional vulnerability to educational adversity, but in the better educated group, Met allele carriers excelled. Our study in Plains American Indians has shown that COMT Val158Met influences several aspects of cognition and some of its effects are moderated by educational adversity.     

The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis

The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of COMT Val158Met polymorphism and prostate cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for COMT Val158Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage (Version 5.0) and Stata (Version 12.0). Six case–control studies, totally 4,118 persons including 2,143 cases and 1,975 controls, met the included criteria and thus were selected. Our analysis suggested that Val158Met polymorphism was associated with prostate cancer risk in overall population. Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002–1.138, P _{heterogeneity} = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057–1.517, P _{heterogeneity} = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961–1.146, P _{heterogeneity} = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894–0.971, P _{heterogeneity} = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08–5.43, P _{heterogeneity} = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.     

Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans

Catechol-O-methyltransferase (COMT) inactivates circulating catechol hormones, catechol neurotransmitters, and xenobiotic catecholamines by methylating their catechol moieties. The COMT gene has been suggested as a candidate gene for schizophrenia through linkage analyses and molecular studies of velo-cardio-facial syndrome. A coding polymorphism of the COMT gene at codon 108/158 (soluble/membrane-bound form) causing a valine to methionine substitution has been shown to influence enzyme activity, but its association with schizophrenia is inconclusive. We have screened 17 known polymorphisms of the COMT gene in 320 Korean schizophrenic patients and 379 controls to determine whether there is a positive association with a nonsynonymous single-nucleotide polymorphism (rs6267) at codon 22/72 (soluble/membrane-bound form) causing an alanine-to-serine (Ala/Ser) substitution. With the Ala/Ala genotype as a reference group, the combined genotype (Ala/Ser and Ser/Ser)-specific adjusted odds ratio was 1.82 (95% CI=1.19–2.76; P=0.005), suggesting the Ser allele as a risk allele for schizophrenia. However, the Val/Met polymorphism was not associated with an increased risk of schizophrenia in Koreans (OR=0.88, 95% CI=0.64–1.21; P=0.43). The Ala72Ser substitution was correlated with reduced COMT enzyme activity. Our results support previous reports that the COMT haplotype implicated in schizophrenia is associated with low COMT expression.     

The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

The Val158Met polymorphism of the COMT gene has been implicated in susceptibility to uterine leiomyoma (ULM), but the reported results were inconclusive. The aim of the study was to evaluate the Val158Met polymorphism of the COMT gene and the risk of ULM by meta-analysis. A comprehensive electronic search for relevant articles was conducted in Pubmed, Embase, CNKI, Wanfang, and Weipu databases. Statistical analysis was performed by using the Revman4.2 software and Stata10.0 software. A total of 7 articles including 12 case–control studies were identified in this meta-analysis. The results showed that the polymorphism was associated with decreased risk of ULM (Met/Met + Val/Met vs. Met/Met: OR = 0.84, 95% CI = 0.70–0.99, Z = 2.07, p = 0.04). In the subgroup analyses by ethnicity, significant decreased risk was found among the black populations (OR = 0.68, 95% CI = 0.48–0.97, Z = 2.15, p = 0.03). The current meta-analysis suggested that the Val158Met polymorphism in the COMT gene was associated with decreased risk of ULM, especially in the black population. Future studies are needed to validate our conclusions.     

Association of MAOA and COMT gene polymorphisms with palatable food intake in children

Several studies have implicated dopamine (DA) in appetite regulation. The enzymes catechol-o-methyltransferase (COMT) and monoamine oxidase A (MAOA) control DA availability and their genes have well-characterized functional variants. In this study, we examined three polymorphisms in these genes, T941G and MAOAu-VNTR in the MAOA gene and Val158Met in the COMT gene, to investigate how heritable variations in enzymes that determine DA levels might influence food intake and nutritional status. This investigation was a cross-sectional examination of 354 Brazilian children of three to four years old. Polymorphisms were analyzed by PCR-based methods. Means of dietary and anthropometric data were compared among genotypes by one-way analyses of variance or Kruskal Wallis tests. The MAOAu-VNTR and COMT Val158Met polymorphisms were associated with the amount of palatable food intake in boys. Presence of the MAOAu-VNTR*long allele was associated with higher intake of lipid-dense foods (LDF) when compared with the *short allele (P=.009); the amount of sugar-dense foods (SDF) intake was also higher in males carriers of the MAOAu-VNTR *long allele than in carriers of the *short allele (P=.034). In the girls' sample, MAOAu-VNTR polymorphism was not associated with food intake and nutritional status. Carriers of the COMT Val158Met*Val allele presented higher intake of LDF when compared with Met/Met homozygotes (P=.008). This study provides the first indication that genetic variants of enzymes that control DA availability might be involved in determination of the amount of palatable food intake in children.     

Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity

In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的：研究儿茶酚胺氧位甲基转移酶（COMT）的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法：应用聚合酶链式反应．限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rsl65599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果：上述4个候选基因中,COMT基因rs737865位点C／C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义（P〈0．05）。其余3个位点统计学分析均无显著性差异（P〉0．05）。单倍型分析：上述四个候选基因构建出12种主要单倍型（每种单倍型在对照组和酒依赖组中的频率至少有一个大于1％）,单倍型A—C—A—A有可能是云南汉族酒精依赖发生的一种危险因子（OR：2．865,P=0．003347）。连锁不平衡分析显示：云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁（D〉0．8）。结论：在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C／C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子。云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

COMT polymorphism modulates the resting‐state EEG alpha oscillatory response to acute nicotine in male non‐smokers

Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists, and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol‐O‐methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting‐state electroencephalographic (EEG) oscillations. In a sample of 62 healthy non‐smoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double‐blind, placebo‐controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in frontocentral regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT.     

Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging

The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的:研究儿茶酚胺氧位甲基转移酶(COMT)的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法:应用聚合酶链式反应-限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rs165599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果:上述4个候选基因中,COMT基因rs737865位点C/C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义(P<0.05)其余3个位点统计学分析均无显著性差异(P>0.05)。单倍型分析:上述四个候选基因构建出12种主要单倍型(每种单倍型在对照组和酒依赖组中的频率至少有一个大于1%),单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子(OR:2.865,P=0.003347)连锁不平衡分析显示:云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁(D>0.8)结论:在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C/C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

Differential Effects of the Catechol-O-Methyltransferase Val158Met Genotype on the Cognitive Function of Schizophrenia Patients and Healthy Japanese Individuals

Background

The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia.

Methods

Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements.

Results

The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia.

Conclusion

These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings.