Under the catalysis of a variety of metabolic enzymes in vivo, such as UDP-glucuronyl transferases, cytochrome P450, carboxylesterase, sulfotransferase, butyrylcholinesterase, catechol-O-methyl transferase and 6-morphine dehydrogenase, the drugs perform glucuronidation, hydrolysis, oxidation, sulfonation and other reactions, then translate into active or inactive metabolites, which are excreted through urination, bile or the other pathways at last. Different drugs own their different metabolic pathways. This paper introduces the studies about the metabolism of drugs in human and animal in recent years, such as morphine-like drugs, amphetamine, ketamine, cannabis and cocaine, and reviews the research progress about the sites of metabolism, metabolic enzymes, metabolites and physiological activity of those drugs metabolic in vivo.
Alcohol Oxidoreductases/metabolism* ; Animals ; Carboxylesterase/metabolism* ; Catechol O-Methyltransferase/metabolism* ; Cholinesterases/metabolism* ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Humans ; Illicit Drugs/metabolism* ; Oxidation-Reduction ; Sulfotransferases/metabolism*

OBJECTIVES: Catecholamine metabolism has been thought to be related to the pathophysiology of panic disorder. There are two human COMT alleles, coding for a low activity enzyme, COMT L(L), and a high activity enzyme, COMT H(H), respectively. We examined the distribution of COMT genotypes and the relationship between COMT genetic polymorphism and some clinical characteristics in patients with panic disorder. METHOD: We recruited 51 patients who met the DSM-IV criteria for panic disorder, and 45 normal control subjects who had neither medical nor psychiatric illnesses. Genetic polymorphism of COMT was identified in all subjects using PCR-based restriction fragment length polymorphism(RFLP) analysis. We assessed some clinical variables including treatment responses in panic patients and measured anxiety and depression levels in normal control subjects using Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). RESULT: The frequency of the homozygous LL genotype was higher in panic patients than that in control subjects (19.6% vs. 2.2%). We found that panic disorder was significantly associated with L allele (x2=8.66, p=0.003) and LL genotype(x2=8.45, p=0.015). Panic patients with LL genotype showed poorer treatment response than those with other genotypes (F=4.98, p=0.011). CONCLUSION: These results suggest that LL genotype of the COMT gene may be related to the pathophysiology and clinical courses in some patients with panic disorder.
Alleles ; Anxiety ; Catechol O-Methyltransferase* ; Clinical Coding ; Depression ; Diagnostic and Statistical Manual of Mental Disorders ; Genotype ; Humans ; Metabolism ; Panic Disorder* ; Panic* ; Pilot Projects* ; Polymorphism, Genetic*

OBJECTIVETo study the expression of the gene and coding protein of catechol o-methyltransferase (COMT) in the colorectal cancer and distant normal mucosa.

METHODSThe tumor tissues and distant normal mucosa of 22 patients with colorectal cancer received surgical treatment from January to August 2009 were collected. Total RNA and protein were extracted and tested using reverse transcription polymerase chain reaction (RT-PCR), Western blot was used to detect the expression of COMT in the tumor tissue and normal mucosa. Tissue array was performed to verify the COMT protein expression. The gray scale scan was used to differentiate the COMT expression level of the mRNA and protein between the two groups.

RESULTSThe tested mean light density of COMT mRNA was 53 514 +/- 15 513 in the tumor tissue group and 4529 +/- 1698 in the normal mucosa group, the expression of COMT gene in colorectal cancer tissue was significantly higher than that in the normal mucosa (P < 0.05). Western blot results showed that the expression level of soluble COMT protein in the colorectal cancer tissue was significantly higher than that in the corresponding distant normal mucosa (mean light density 54 967 +/- 11 919 vs. 25 962 +/- 6713) (P < 0.05), but the expression of membrane-bound COMT protein was not statistically different between the two groups. Tissue array revealed that the COMT protein mainly located in the cytoplasm, and it was significantly over-expressed in the colorectal cancer tissue than in the normal mucosa (P < 0.05).

CONCLUSIONSThe COMT gene and encoding protein is over-expressed in the colorectal cancer tissue than in the distant normal mucosa. The COMT gene might be involved in the biological behavior of the colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Catechol O-Methyltransferase ; genetics ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; genetics

OBJECTIVETo detect the relationship between heroin-dependence and -287 A/G polymorphism of catechol-O-methyltransferase(COMT) gene.

METHODSGenotype and allele frequencies of -287 A/G polymorphism of COMT gene were examined in 268 heroin-dependent subjects and 177 normal controls.

RESULTSWeak but significant difference in genotype of -287 A/G polymorphism of COMT gene was observed between heroin-dependent subjects and controls (chi(2)=7.41, P=0.025), and genotype AA was higher in the former. The frequency of allele A of -287 A/G polymorphism of COMT gene was also significantly higher in heroin-dependent subjects than in the controls (chi(2)=5.69, P=0.017).

CONCLUSIONThe results suggested that liability to heroin-dependence was associated with -287 A/G polymorphism of COMT gene.

Adolescent ; Adult ; Alleles ; Catechol O-Methyltransferase ; genetics ; DNA ; genetics ; metabolism ; DNA Restriction Enzymes ; metabolism ; Female ; Gene Frequency ; Genotype ; Heroin Dependence ; enzymology ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics

BACKGROUND: Recent genetic association studies have investigated the possible genetic role of the dopaminergic system in migraine. Catechol-O-methyltransferase (COMT) is an enzyme that plays a crucial role in the metabolism of dopamine and its genetic polymorphism is associated with three- to fourfold variation of enzymatic activity. OBJECTIVES: The objective of this study was to elucidate the role of the COMT polymorphism in the genetic susceptibility to migraine and its phenotypic expression in patients with migraine without aura (MWOA). METHODS: Ninety-seven patients with MWOA and 94 healthy volunteers were included in the study. After amplifying COMT genes by the polymerase chain reaction, we assessed their genotype frequencies and allele distributions by based on restriction fragment length polymorphisms. We classified all MWOA patients into two groups according to their COMT genotype: with the L allele (N = 43), and without this allele (N = 54). RESULTS: The genotype frequency and allele distribution of the COMT polymorphism did not differ between MWOA patients and the control group. During migraine attacks, MWOA patients with the L allele showed a higher pain intensity of headache (P = 0.001) and a higher incidence of the accompanying nausea/vomiting (94% vs 75%; P = 0.026) compared with MWOA patients without the L allele. CONCLUSIONS: Although the COMT polymorphism does not appear to be involved in predisposition to the development of MWOA, this genetic factor could be involved in the phenotypic expression of MWOA.
Alleles ; Catechol O-Methyltransferase* ; Dopamine ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Headache ; Healthy Volunteers ; Humans ; Incidence ; Metabolism ; Migraine Disorders* ; Migraine without Aura* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

BACKGROUND AND OBJECTIVEGenetic polymorphism Val158Met of catechol-O-methyltransferase (COMT) may contribute to estrogen-induced carcinogenesis of breast cancer. Soy isoflavones possesses chemical structure similar to endogenous estrogen and may promote the carcinogenesis of breast cancer. This study was to investigate the relationship between the polymorphism of COMT, soy isoflavones, and breast cancer in postmenopausal women.

METHODSIn total, 176 patients newly diagnosed histopathologically with breast cancer were recruited from May 2007 to July 2009, and 176 age-matched cancer-free women as controls were selected from a community-based physical check-up population at the same period. The food-frequency questionnaire was used to collect information on soy food intake. Allele-specific polymerase chain reaction (AS-PCR) was employed to analyze genetic polymorphism Val158Met of COMT. Adjusted odd ratios (aORs) and 95% confidence intervals (95% CI) were estimated by multivariable nonconditional logistic regression.

RESULTSThe proportion of susceptible genotype (COMT-LL) in breast cancer patients was significantly higher than that in the controls. After adjusting selected risk factors, the aOR and 95% CI of COMT-LL were 3.14 (1.48-6.66) as compared with those of COMT-HH genotype. The intake of soy isoflavones had a negative correlation with breast cancer in a dose-dependent manner (Chi2 = 28.26, P < 0.001). The women with high intake of soy isoflavones (> or = 16.26 mg/d) and carrying susceptible genotype (COMT-LL), as compared with the women carrying the COMT-HH + COMT-HL genotypes and consuming low level of soy isoflavones (< 16.26 mg/d), had no significantly increased risk for breast cancer [ aOR (95% CI) = 1.66 (0.52-5.24)].

CONCLUSIONSIn postmenopausal women, carrying COMT-LL genotype may increase the risk for breast cancer, and soy isoflavones intake may protect them from breast cancer. But there may be no interaction between intake of soy isoflavones and COMT-LL genotype.

Adult ; Aged ; Breast Neoplasms ; genetics ; Case-Control Studies ; Catechol O-Methyltransferase ; genetics ; metabolism ; Codon ; Confidence Intervals ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Isoflavones ; administration & dosage ; Middle Aged ; Odds Ratio ; Polymorphism, Genetic ; Postmenopause ; Risk Factors ; Soy Foods

Catechol-O-methyltransferase (COMT) gene encodes catechol-O-methyltransferase, the variant of this gene may affect the expression and metabolic activity of COMT. As the result of the changes of the effective concentration of the catecholamine neurotransmitter in the central nervous system, central nervous system dysfunctions associated with schizophrenia. This review summarizes genetic polymorphism and diversity of COMT gene. It also elaborates the relation between SNP and haplotype of COMT gene and three aspects, which including schizophrenia, attacking and violent tendency, and the frontal cognitive function of the schizophreniac. The correlativity study between genetic variation of the COMT gene and schizophrenia in patients with attacking and violent tendency may be helpful for the assessment of forensic psychiatry.
Aggression/psychology* ; Brain/pathology* ; Catechol O-Methyltransferase/genetics* ; Cognition/physiology* ; Dopamine/metabolism* ; Forensic Genetics ; Gene Expression ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prefrontal Cortex/pathology* ; Promoter Regions, Genetic ; Schizophrenia/genetics* ; Violence/psychology*

OBJECTIVE: To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section. METHODS: A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors. RESULTS: The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression. CONCLUSIONS The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.
Catechol O-Methyltransferase ; genetics ; Cesarean Section ; adverse effects ; Depression, Postpartum ; diagnosis ; enzymology ; genetics ; Domestic Violence ; psychology ; Female ; Gene-Environment Interaction ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Monoamine Oxidase ; genetics ; Norepinephrine ; metabolism ; Polymorphism, Single Nucleotide ; Postoperative Complications ; diagnosis ; enzymology ; genetics ; Pregnancy ; Pregnancy Complications ; etiology ; psychology ; Risk Factors ; Stress, Psychological