ABSTRACT
The alluring properties of a luminescent graphene quantum dot (GQD)-based nanocomposite are unquestionable to realize many advanced applications, such as sweat pH sensors. The well-suited hydrophilic polymers to host GQDs can face an unavoidable swelling behavior, which deteriorates the mechanical stability, whereas the hydrophobic polymers can prevent swelling but at the same time barricade the analyte pathways to GQDs. To resolve the two aforementioned obstacles, we develop a nanocomposite film containing nitrogen-doped GQDs (NGQDs) incorporated into a transparent, elastic, and self-healable polymer matrix, composed of a hydrophobic n-butyl acrylate segment and a hydrophilic N-(hydroxymethyl)acrylamide segment for wearable healthcare pH sensors on the human body. Besides serving as the fluorescence source, NGQDs are also designed as a nano-cross-linker to promote abundant chemical and physical interactions within the nanocomposite network. This synergetic effect gives rise to a 10-fold higher mechanical strength, 7-fold increment in Young's modulus, 4-fold increment in toughness, and 15-fold more sensitivity in pH detection (pH 3-10) compared to those of the pristine copolymer and NGQDs, respectively. Moreover, the mechanically enhanced nanocomposite possesses a high self-healing efficiency (94%) at room temperature even under water and demonstrates a stable sensing performance after repetitive usage for 30 days. Our work provides insights into the simple preparation of human skinlike nanocomposite elastomers usable for wearable pH sensors.
ABSTRACT
OBJECTIVE: To investigate surgical skills and clinical effects of manipulative reduction and percutaneous Kirschner wire internal fixation in treating grade IV supination-external rotation ankle fractures. METHODS: From May 2013 to October 2016, 35 patients with grade IV supination-external rotation ankle fractures were treated with percutaneous Kirschner wire internal fixation, involving 22 males and 13 females with an average age of 38.2 years ranged from 18 to 65 years old. The time from injury to operation ranged from 2 h to 10 d with an average of 5 d. Reduction quality was assessed by Burwell-Charnley radiological criteria. Baird-Jackson ankle scoring system was used to assess clinical effects. RESULTS: Thirty-three patients were followed up from 10 to 28 months with an average of 14 months. Fracture healing time ranged from 10 to 18 weeks with an average of 12 weeks. According to Burwell-Charnley radiological criteria, 30 cases were obtained anatomic reduction, 3 cases moderate. According to Baird-Jackson ankle scoring system, total score was 93.8±5.4, 17 cases got excellent result, 12 good, 2 fair and 2 poor. CONCLUSIONS: Manipulative reduction and percutaneous Kirschner wire internal fixation in treating grade IV supination-external rotation ankle fractures has advantages of reliable efficacy, less complications. But higher require techniques were required for closed reduction. It is not suitable for severe crushed fracture and compressive articular surface fracture.
Subject(s)
Ankle Fractures/surgery , Bone Wires , Fractures, Bone/surgery , Adult , Aged , Ankle Fractures/pathology , Ankle Injuries/surgery , Female , Fracture Fixation/methods , Fracture Fixation, Internal , Fractures, Bone/pathology , Humans , Male , Middle Aged , Musculoskeletal Manipulations/methods , Rotation , Supination , Treatment OutcomeABSTRACT
It is hypothesized that dopaminergic genes-dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)-are associated with bipolar disorder (BP) and anxiety disorder (AD). Bipolar II (BP-II) is reported to be highly comorbid with AD. We examined whether interactions among these three genes are susceptibility factors in BP-II with AD (BP-II(+AD)) and without AD (BP-II(-AD)). In this study, we hypothesize that the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different. We recruited 1260 participants: 495 with BP-II(-AD), 170 with BP-II(+AD), and 595 healthy controls without BP-II or AD. Genotyping was done using polymerase chain reactions plus restriction fragment length polymorphism analysis. Genotypic frequencies of the DRD2TaqIA, COMT, and ALDH2 polymorphisms between the two BP-II groups were nonsignificant. In logistic regression, the ALDH2 and DRD2TaqIA genes showed a main effect that was protective against BP-II(-AD) (odds ratio [OR] = 0.497, p = 0.010, and OR = 0.415, p = 0.017, respectively). The interaction of DRD2TaqIA A1/A1 and ALDH2*1/*1 had a significant risk effect on the BP-II(-AD) group (OR = 7.177, p < 0.001). However, the interaction of DRD2TaqIA A1/A1, ALDH2*1/*1, and COMTMet/Met&Val/Met become a weak protective factor against BP-II(-AD) (OR = 0.205, p = 0.047). All of the significant results described above are found only in BP-II(-AD). This study supports the hypothesis the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different,, and provides additional evidence that the DRD2TaqIA A1/A1, ALDH2*1/*1 and COMT genes interact in BP-II(-AD) but not in BP-II(+AD).
Subject(s)
Aldehyde Dehydrogenase/genetics , Anxiety Disorders/genetics , Asian People/genetics , Bipolar Disorder/genetics , Catechol O-Methyltransferase/genetics , Receptors, Dopamine D2/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Bipolar Disorder/diagnosis , Bipolar Disorder/epidemiology , Comorbidity , Epistasis, Genetic/genetics , Female , Humans , Male , Middle Aged , Taiwan/epidemiology , Young AdultABSTRACT
Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1ß was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α.
Subject(s)
Dental Pulp/metabolism , Inflammation Mediators/metabolism , MAP Kinase Signaling System , NF-kappa B/metabolism , Proto-Oncogene Proteins/metabolism , Wnt Proteins/metabolism , Animals , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Dental Pulp/pathology , Female , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Macrophages/metabolism , Macrophages/pathology , Male , NF-kappa B/genetics , Proto-Oncogene Proteins/genetics , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Wnt Proteins/genetics , Wnt-5a ProteinABSTRACT
Memantine is a non-competitive N-methyl-d-asparate (NMDA) receptor antagonist with a mood-stabilizing effect. We investigated whether using valproic acid (VPA) plus add-on memantine to treat bipolar II disorder (BP-II) is more effective than using VPA alone (VPA + Pbo). We also evaluated, in BP-II patients, the association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with treatment response to VPA + add-on memantine and to VPA + Pbo. In this randomized, double-blind, controlled 12 wk study, BP-II patients undergoing regular VPA treatments were randomly assigned to a group: VPA + Memantine (5 mg/day) (n = 115) or VPA + Pbo (n = 117). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response during week 0, 1, 2, 4, 8 and 12. The genotypes of the BDNF Val66Met polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. To adjust within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used to analyze the effects of the BDNF Val66Met polymorphism on the clinical performance of memantine. Both groups showed significantly decreased YMRS and HDRS scores after 12 wk of treatment; the differences between groups were non-significant. When stratified by the BDNF Val66Met genotypes, significantly greater decreases in HDRS scores were found in the VPA + memantine group in patients with the Val Met genotype (p = 0.004). We conclude that the BDNF Val66Met polymorphism influenced responses to add-on memantine by decreasing depressive symptoms in patients with BP-II.
Subject(s)
Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Brain-Derived Neurotrophic Factor/genetics , Genetic Variation/genetics , Memantine/administration & dosage , Valproic Acid/administration & dosage , Adult , Bipolar Disorder/diagnosis , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Polymorphism, Genetic/genetics , Young AdultABSTRACT
Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5-HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.
Subject(s)
Bipolar Disorder/genetics , Genetic Variation/genetics , Receptors, Dopamine D2/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Sex Characteristics , Adult , Asian People/ethnology , Asian People/genetics , Bipolar Disorder/diagnosis , Bipolar Disorder/ethnology , Female , Humans , Male , Middle Aged , Polymorphism, Genetic/genetics , Taiwan/ethnology , Young AdultABSTRACT
The vulnerability of developing addictions is associated with genetic factors and personality traits. The predisposing genetic variants and personality traits may be common to all addictions or specific to a particular class of addiction. To investigate the relationship between genetic variances, personality traits, and their interactions in addiction are important. We recruited 175 opiate-dependent patients, 102 alcohol-dependent patients, and 111 healthy controls. All participants were diagnosed using DSM-IV criteria and assessed with Tridimensional Personality Questionnaire (TPQ). The dopamine D2 receptor (DRD2), 5-HTT-linked promoter region (5-HTTLPR), and aldehyde dehydrogenase 2 (ALDH2) genes were genotyped using PCR. The genotype frequency of the 5-HTTLPR and ALDH2 was significantly different between the patients and controls (P=0.013, P<0.001, respectively), and borderline significant (P=0.05) for DRD2 polymorphism. Both Novelty Seeking (NS) and Harm Avoidance (HA) scores were higher for patients (P<0.001). After stratification by candidate genes, addicts with ALDH2 *1/*1 interacting with the low-functional group of DRD2 and 5-HTTLPR genes have higher HA traits, whereas addicts with ALDH2 *1/*2 or *2/*2 and low-functional group of DRD2 and 5-HTTLPR genes have higher NS traits. We concluded that addicts, both alcohol- and opiate-dependent patients, have common genetic variants in DRD2 and 5-HTTLPR but specific for ALDH2. Higher NS and HA traits were found in both patient groups with the interaction with DRD2, 5-HTTLPR, and ALDH2 genes. The ALDH2 gene variants had different effect in the NS and HA dimension while the DRD2 and 5-HTTLPR genes did not.
Subject(s)
Alcoholism/genetics , Aldehyde Dehydrogenase/genetics , Opioid-Related Disorders/genetics , Personality/genetics , Receptors, Dopamine D2/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Alcoholism/psychology , Aldehyde Dehydrogenase, Mitochondrial , Analysis of Variance , Case-Control Studies , Female , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Opioid-Related Disorders/psychology , Personality Inventory , Polymorphism, Genetic , Psychiatric Status Rating Scales , TaiwanABSTRACT
OBJECTIVES: Heroin dependence is a multifactor disorder. We investigated the association of genetic factors and heroin-dependent temperaments to determine whether a temperament-gene interaction is involved in the pathogenesis of heroin dependence. METHODS: Three hundred seventy participants (259 heroin-dependent patients and 111 healthy controls) were recruited and finished the Tridimensional Personality Questionnaire to assess personality traits (temperament). The genotypes of the aldehyde dehydrogenase 2 (ALDH2) gene and the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Multiple logistic regression analysis showed significant main effects for novelty seeking (P ≤ 0.001) and harm-avoidance (P = 0.001) scores, and a significant interaction effect between novelty seeking and ALDH2 genotypes (P = 0.016) in heroin-dependent patients compared with controls. When stratified by the ALDH2 genotypes, only heroin-dependent patients with the *1*2 and *2*2 genotypes at ALDH2 had higher novelty-seeking scores than did controls (heroin dependence = 15.94, controls = 12.46; P ≤ 0.001). CONCLUSIONS: Our results provide initial evidence that the ALDH2 gene interacted with novelty seeking in heroin-dependent Han Chinese patients in Taiwan.
Subject(s)
Aldehyde Dehydrogenase/genetics , Brain-Derived Neurotrophic Factor/genetics , Exploratory Behavior , Heroin Dependence/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Case-Control Studies , Female , Genotype , Humans , Logistic Models , Male , Middle Aged , Personality Inventory , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Surveys and Questionnaires , TaiwanABSTRACT
BACKGROUND: Several studies have hypothesized that genes involved in the dopamine system, including dopamine type-2 receptor (DRD2)-related TaqIA polymorphism and monoamine oxidase-A upstream variable number tandem repeat (uVNTR), may be associated with alcoholism. But their results were contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the DRD2TaqIA and MAOA-uVNTR gene polymorphisms are susceptibility factors for alcoholism comorbid with bipolar disorder (ALC+BP) in Han Chinese in Taiwan. METHODS: We recruited 101 Han Chinese men with comorbid alcoholism and bipolar disorder, and 328 healthy male controls from the community. Genotyping was done using PCR-RFLP. RESULTS: There were no significant differences in the genotypic frequencies of the DRD2TaqIA or the MAOA-uVNTR polymorphisms between the 2 groups. The MAOA-uVNTR 3-repeat had a significant protective effect on the ALC+BP (odds ratio=0.432, p=0.035) but not on the healthy controls. However, the interaction between the MAOA-uVNTR 3-repeat and DRD2 A1/A2 was a risk factor in the ALC+BP (odds ratio=3.451, p=0.018). CONCLUSIONS: We indicated the impact of the association between MAOA-uVNTR 3-repeat and DRD2 A1/A2 with ALC+BP.
Subject(s)
Alcoholism/genetics , Bipolar Disorder/genetics , Monoamine Oxidase/genetics , Receptors, Dopamine D2/genetics , Adult , Alcoholism/epidemiology , Alleles , Asian People/genetics , Bipolar Disorder/epidemiology , China/epidemiology , Comorbidity , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Polymorphism, GeneticABSTRACT
Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.
Subject(s)
Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase/genetics , Heroin Dependence/genetics , Polymorphism, Genetic/genetics , Receptors, Dopamine D2/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Alleles , Data Interpretation, Statistical , Female , Gene Frequency , Genotype , Heroin Dependence/epidemiology , Humans , Logistic Models , Male , Risk , Taiwan/epidemiologyABSTRACT
OBJECTIVE: Clarifying the similarities and differences between the two most common subtypes of bipolar disorder, bipolar-I and bipolar-II, is essential for improving our understanding of them. Because the serotonergic system has been implicated in the pathogenesis of bipolar disorder, it may be important to investigate genes such as the aldehyde dehydrogenase 2 (ALDH2) and serotonin 2A receptor genes, which are involved in metabolizing serotonin and encoding serotonin receptors. We examined the association of the ALDH2 and 5-HT2A-A1438G polymorphisms with bipolar I and II and possible interactions between these genes. METHODS: One thousand forty-nine participants were recruited: 249 with bipolar-I, 456 with bipolar-II, and 344 healthy controls. The genotypes of the ALDH2 and 5HT2A-A1438G polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Logistic regression analysis showed a significant effect of the ALDH2 and the 5-HT2A-A1438G polymorphisms, and a significant interaction effect for the A/G genotypes of the 5-HT2A-A1438G polymorphism and the ALDH2*1*1 genotypes (p=0.004) discriminated between bipolar-I patients and controls without bipolar disorder. These polymorphisms, however, were not associated with bipolar-II disorder. LIMITATIONS: The significant differences of age and gender between patients and controls limit the comparison, although statistical adjustments were made for them. CONCLUSION: Our findings provide initial evidence that the ALDH2 and 5-HT2A genes interact in bipolar-I but not in bipolar-II disorder. Our findings suggest a unique genetic distinction between bipolar-I and bipolar-II.
Subject(s)
Aldehyde Dehydrogenase/genetics , Bipolar Disorder/genetics , Receptor, Serotonin, 5-HT2A/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Bipolar Disorder/classification , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment LengthABSTRACT
BACKGROUND: Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. METHODS: We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n=120) and antisocial non-alcoholism (AS-N-ALC) group (n=153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. RESULTS: There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. CONCLUSION: Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan's Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.
Subject(s)
Alcoholism/genetics , Antisocial Personality Disorder/genetics , Asian People/genetics , Receptor, Serotonin, 5-HT1B/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Alcoholism/ethnology , Antisocial Personality Disorder/ethnology , Asian People/statistics & numerical data , Comorbidity , Genetic Predisposition to Disease/ethnology , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Polymorphism, Genetic/genetics , Risk Factors , Taiwan/epidemiology , Young AdultABSTRACT
Dextromethorphan (DM) is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that may be neuroprotective for monoamine neurons. We hypothesized that adding DM to valproate (VPA) treatment would attenuate bipolar disorder (BP) symptoms. We evaluated in BP patients the association between the DRD2/ANKK1 TaqIA polymorphism with treatment response to VPA+add-on DM and to VPA+placebo. This double-blind, stratified, randomized study ran from January 2007 through December 2010. BP patients undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (60 mg/day) (n=167) or placebo (n=83) for 12 weeks. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate clinical response. The genotypes of the DRD2/ANKK1 TaqIA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. To adjust within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used to analyze the effects of the DRD2/ANKK1 TaqIA polymorphism on clinical performance. Both groups showed significantly decreased YMRS and HDRS scores after 12 weeks of treatment; the differences between groups were non-significant. Decreases in YMRS scores were greater in patients with the A1A1 (P=0.004) genotypes than with the A2A2 genotype. We conclude that the DRD2/ANKK1 TaqIA polymorphism influenced responses to DM by decreasing manic symptoms in BP patients.
Subject(s)
Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Dextromethorphan/therapeutic use , Neuroprotective Agents/therapeutic use , Protein Serine-Threonine Kinases/genetics , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Adult , Antimanic Agents/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Genotype , Humans , Male , Polymorphism, Genetic , Receptors, Dopamine D2/genetics , Valproic Acid/therapeutic use , Young AdultABSTRACT
BACKGROUND: Determining the influences of genes involved in metabolizing dopamine and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) genes, is critical for understanding addictive behavior. Therefore, we investigated the association between the ALDH2 and DRD2/ANKK1 Taq IA polymorphisms and heroin dependence. METHODS: Heroin-dependent Han Chinese patients (250) and healthy controls (312) were recruited. ALDH2 and DRD2/ANKK1 Taq IA polymorphisms were genotyped. RESULTS: The frequency of ALDH2*1/*2 and *2/*2 genotypes was significantly higher in heroin-dependent patients than in controls, but the frequency of DRD2 Taq IA genotypes was not significantly different. Logistic regression analysis showed no significant interaction between ALDH2 and DRD2 Taq IA genotypes in patients. CONCLUSIONS: The ALDH2 polymorphism, but not the DRD2, was associated with heroin dependence.
Subject(s)
Aldehyde Dehydrogenase/genetics , Heroin Dependence/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Alleles , Case-Control Studies , Female , Genetic Association Studies , Genotype , Humans , Logistic Models , Male , Polymorphism, Genetic/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Dopamine D2/geneticsABSTRACT
BACKGROUND: Whether bipolar II disorder is a distinct disorder or simply a milder form of bipolar I disorder has been debated. Family, twin, and adoption studies provide robust evidence of genetic contributions to bipolar disorder, and heritable temperaments are also believed to contribute to the susceptibility to bipolar disorders. In this study, we sought to clarify the relationship between bipolar I and bipolar II disorder. METHOD: In this cross-sectional survey, 314 participants (82 bipolar I disorder patients, 121 bipolar II disorder patients, and 111 healthy controls) completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Tridimensional Personality Questionnaire, which assessed the personality dimensions of novelty seeking and harm avoidance. We also determined which participants carried the serine-to-glycine substitution at amino acid position 9 polymorphism of the dopamine D3 receptor gene (DRD3) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotypes. All patients met the DSM-IV-TR diagnosis criteria for bipolar disorder. This study was conducted from September 2005 to July 2009 at National Cheng Kung University Hospital, Tainan, Taiwan, and Tri-Service General Hospital, Taipei, Taiwan. RESULTS: Binary logistic regression analysis showed significant main effects for the 5-HTTLPR polymorphism (P = .045), novelty seeking (P = .022), and harm avoidance (P = .017) scores and a significant interaction effect between harm avoidance and 5-HTTLPR genotypes (P = .042) in distinguishing between bipolar I and bipolar II disorder patients. Bipolar I disorder patients with the long allele at 5-HTTLPR had lower harm avoidance scores than did bipolar II disorder patients (bipolar I disorder = 16.23, bipolar II disorder = 19.80; P = .023); however, the difference was not significant after multiple test correction. All these data suggest a distinction between bipolar I and bipolar II disorder. CONCLUSIONS: We provide initial evidence that 5-HTTLPR genotypes might moderate the association between harm avoidance and bipolar I and bipolar II disorder. There appear to be unique differences in the gene-temperament interactions of bipolar I and bipolar II disorder patients.
Subject(s)
Asian People/genetics , Asian People/psychology , Bipolar Disorder/genetics , Bipolar Disorder/psychology , Receptors, Dopamine D3/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Temperament , Adult , Alleles , Bipolar Disorder/diagnosis , Cross-Sectional Studies/statistics & numerical data , Female , Genotype , Health Surveys/statistics & numerical data , Humans , Male , Personality Inventory/statistics & numerical data , Polymorphism, Single NucleotideABSTRACT
OBJECTIVES. Clarifying the association between bipolar I and bipolar II disorders at the genetic level is essential for improving our understanding of them. In this study, we evaluated the hypothesis that the dopaminergic polymorphisms are risk factors for bipolar disorders. We examined the association between the catechol-O-methyltransferase (COMT) Val158Met and dopamine D3 receptor (DRD3) Ser9Gly polymorphisms and bipolar I and II disorders, as well as possible interactions between these genes. METHODS. Seven hundred and eleven participants were recruited: 205 with bipolar I, 270 with bipolar II, and 236 healthy controls. The genotypes of the COMT Val158Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS. Logistic regression analyses showed a statistically significant main effect for the Met/Met genotype of the COMT Val158Met polymorphism (P=0.032) and a significant interaction effect for the Met/Met genotype of the COMT Val158Met and Ser/Ser genotypes of the DRD3 Ser9Gly polymorphism (P=0.001) predicted bipolar I patients. However, there was no association between the COMT Val158Met or DRD3 Ser9Gly and bipolar II. CONCLUSIONS. We provide initial evidence that the COMT Val158Met and DRD3 Ser9Gly genotypes interact in bipolar I and bipolar II disorders and that bipolar I and bipolar II are genetically distinct.
Subject(s)
Bipolar Disorder/genetics , Catechol O-Methyltransferase/genetics , Receptors, Dopamine D3/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Genes/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Logistic Models , Male , Polymorphism, Single Nucleotide/geneticsABSTRACT
AIM: Clarifying the association between bipolar I and bipolar II, the two most common subtypes of bipolar disorder, at the genetic level is essential for improving our understanding of these disorders. The dopaminergic system has been implicated in the pathogenesis of bipolar disorder. It may be important to investigate genes involved in metabolizing dopamine and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) genes. We examined the association of the ALDH2 and DRD2/ANKK1 Taq IA polymorphisms with bipolar I and II disorders and possible interactions between these genes. METHODS: Seven hundred and fifty participants were recruited: 207 with bipolar I disorder, 277 with bipolar II disorder, and 266 healthy controls. The genotypes of the ALDH2 and DRD2/ANKK1 TaqIA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Logistic regression analysis showed a statistically significant interaction for the A1/A1 genotype of the DRD2/ANKK1 TaqIA, and the ALDH2*1*1 genotypes (P=0.009) could predict bipolar II patients compared with individuals without bipolar disorder. However, there was no association between the ALDH2 or DRD2/ANKK1 gene with neither bipolar I nor bipolar II disorder. CONCLUSION: Our findings may provide initial evidence that the ALDH2 and DRD2/ANKK1 genes interact in specific subtypes of bipolar disorders. Our findings also suggest a unique genetic distinction between bipolar I and bipolar II disorders.
Subject(s)
Aldehyde Dehydrogenase/genetics , Bipolar Disorder/classification , Bipolar Disorder/genetics , Epistasis, Genetic , Protein Serine-Threonine Kinases/genetics , Receptors, Dopamine D2/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Bipolar Disorder/enzymology , Female , Genotype , Humans , Logistic Models , MaleABSTRACT
BACKGROUND: Several studies have suggested that the serotonin receptor 1B gene (5HT1B) may be important in the pathogenesis of alcohol dependence (alcoholism; ALC; AD). We examined whether 5HT1B gene A-161T polymorphisms (rs130058) are a susceptibility factor for total AD and subgroups of AD. We further explored correlation of this 5HT1B gene variant between anxiety-depression alcoholism (ANX/DEP ALC) and antisocial alcoholism (antisocial ALC) subgroups because of the high comorbidity of anxiety-depression, antisocial personality disorder, and AD. METHODS: We recruited 522 Han Chinese in Taiwan for this study: 322 AD patients and 200 controls. The patient group was recruited primarily from medical teaching hospitals; patients with antisocial alcoholism were recruited from Taiwanese prisons. Individuals with AD were classified into 3 homogeneous clinical subgroups -- pure alcoholism (pure ALC), ANX/DEP ALC, and antisocial ALC -- using DSM-IV diagnosis. The 5HT1B gene A-161T polymorphism was determined using PCR-RFLP. RESULTS: No significant differences in genotypic and allelic frequencies were found between controls and the total AD group or between controls and the 3 AD subgroups. However, there were significant differences in the 5HT1B gene A-161T polymorphism at both the genotype and allelic levels between the ANX/DEP ALC and antisocial ALC subgroups. CONCLUSIONS: This study suggests that the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either AD or its subtypes. However, 5HT1B gene A-161T polymorphisms might be one of the common genetic factors between the ANX/DEP ALC and antisocial ALC subgroups.