COMT Polymorphisms Research Articles

Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders.

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders

Comparative study of the efficacy of dexmedetomidine and fentanyl on anxiety and pain of parturients with different COMTva1158met genotypes

ObjectiveThis study investigates the effects of COMTval158met gene polymorphism on maternal anxiety and pain during delivery and on the analgesic and anxiety efficacy of dexmedetomidine during delivery.MethodsSixty-one pregnant women, who were hospitalized in our hospital from January to November of 2016 were recruited and randomly divided into two groups, F and D groups. The pregnant women in the F group were given labor analgesia with ropivacaine combined with fentanyl. The pregnant women in the D group were given labor analgesia with ropivacaine combined with dexmedetomidine. Before and after labor analgesia, the genotype of COMT in the blood from two groups was detected, and the situation of labor anxiety and analgesia was analyzed. Then, the relationship between labor anxiety, analgesia, and COMT polymorphism was analyzed.ResultsIn the 61 pregnant women, there were 30 women of wild homozygotes (GG) of COMT, 22 women of mutant heterozygotes (GA), and nine women of mutant homozygotes (AA), the mutation rate of allele A was 23.77%. The anxiety status score, anxiety trait score, and pain score in the AA genotype were significantly higher than those in the GG and GA genotype (p < 0.05). There was a significant difference in the efficacy of GG and AA genotypes between groups D and F for treating labor anxiety (p < 0.05), the efficacy of group D was better than that of group F in treating delivery anxiety, there was no significant difference in anxiety scores between the two groups in GA genotypes (p > 0.05); there was no significant difference in pain between group D and F in GG, GA, and AA genotypes (p > 0.05). There was no significant difference in pain and anxiety scores between the three genotypes in group D (p > 0.05), there was significant difference in pain scores among the three genotypes in group F (p < 0.05), but there was no significant difference in anxiety (p > 0.05).ConclusionsThe mutation of the COMTval158met gene leads to increased anxiety and pain during childbirth. The effect of dexmedetomidine on the anxiety of GG and AA genotypes is better than that of fentanyl, and the mutation of the COMTval158met gene has no impact on dexmedetomidine effect.

The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender.

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Effects of DRD2/ANKK1 and COMT Val158Met polymorphisms on stabilization against and adaptation to unexpected events.

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.

Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson's Disease.

Identification of individual risk factors for motor complications in Parkinson's disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOBCC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089–0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039–0.520]; p=0.003) than MAOBTT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD.

Recognition of Emotional and Neutral Visual Scenes in Carriers of the MAOA, COMT, DRD4, and 5HT2A Gene Polymorphisms

It is known that some genes regulate neurochemical metabolism, and their polymorphisms affect cognitive performance, including the ability to categorize emotionally significant information. The aim of our study was to analyze the recognition of emotional and neutral visual scenes in carriers of different polymorphic variants of the MAOA, COMT, DRD4, and 5HT2A genes. The study sample consisted of 87 university students (Caucasians, women 63%, average age 20.4±2.6 years). The genotypes of the COMT, 5HT2A, and DRD4 genes were determined by polymerase chain reaction. Agarose gel electrophoresis was used to determine the number of tandem repeats of the MAOA gene. Three hundred sixty (360) photographic images of scenes of different emotional valence (positive, negative, and neutral - 120 images for each category) were used as stimuli. These images were classified by expert assessments. The images were presented in a random sequence. The exposure time was 700 ms. The research participants were asked to determine the emotional valence of each scene. We found that only the COMT gene genotype affected the recognition of emotional and neutral visual scenes. Carriers of the COMT Val/Val genotype, which causes dopamine to stay in the synaptic space for a shorter time, are better in recognizing and demonstrate higher sensitivity to the emotional content of scenes. Carriers of the Val/Met genotype demonstrated the worst ability to differentiate the emotional valence of visual scenes. This study has shown that the length of stay of monoamines in the synaptic space regulated by the COMT gene affects the recognition of emotional visual information.

Effects of polymorphisms of COMT, TPH1 and SERT gene mutations on perceived childhood trauma in suicide attempters with eating disorders

Effects of polymorphisms of COMT, TPH1 and SERT gene mutations on perceived childhood trauma in suicide attempters with eating disorders

Initial Study on COMT and DRD2 Gene Polymorphisms as Well as the Influence of Temperament and Character Trait on the Severity of Alcohol Craving in Alcohol-Dependent Patients.

The main aim of this work was to determine the impact of COMT and DRD2 gene polymorphisms together with temperament and character traits on alcohol craving severity alcohol-dependent persons. The sample comprised of 89 men and 16 women (aged ). For the sake of psychological assessment various analytic methods have been applied like the Short Alcohol Dependence Data Questionnaire (SADD), Penn Alcohol Craving Scale (PACS) or Temperament and Character Inventory (TCI) test. The SNP polymorphism of the analyzed genes was determined by Real Time PCR test. The results showed, that the COMT polymorphismmay have an indirected relationship with the intensity and changes in alcohol craving during abstinence. The DRD2 receptor gene polymorphisms are related with the intensity of alcohol craving. It seems that the character traits like “self-targeting”, including “self-acceptance”, are more closely related to the severity of alcohol craving and polymorphic changes in the DRD2 receptor than temperamental traits. Although this is a pilot study the obtained results appeared to be promising and clearly indicate the link betweengene polymorphisms alcohol craving and its severity.

Polymorphisms of the KCNS1, COMT and OPRM1 genes and development of postoperative pain in patients with osteoarthritis who underwent total knee or hip replacement

Postoperative pain (POP) is a serious complication that reduces the result of total knee (TKA) or hip arthroplasty (THA) in patients with osteoarthritis (OA). The search for predictors of postoperative pain is an actual problem.The aim of the study – to assessing relationship the polymorphisms of the KCNS1, COMT and OPRM1 genes and the development of POP in OA patients who underwent TKA or THA.Material and methods. The study group consisted of 95 patients with OA knee or hip (64.6% of women, 65.4±9.0 years) who underwent TKA (47.8%) or THA (52.2%). The presence of POP was determined when pain in the area of surgical intervention ≥40 mm (100 mm visual analog scale, VAS) persisted or appeared 3 and 6 months after surgery. All patients underwent genotyping of polymorphisms of the genes KCNS1 (rs734784), COMT (rs6269, rs4633) and OPRM1 (rs1799971) by polymerase chain reaction in real time using original sequence-specific primers and samples labeled with various fluorescent labels. Registration and interpretation of the obtained results were carried out on the DT-96 amplifier (DNA-Technology LLC, Russia).Results. POP was observed in 32.6% of patients who underwent TKA or THA. The frequency of POP after TKA and THA was 30.2% and 34.0% (p=0.882). Statistical analysis revealed no differences in the frequencies of the genotypes of the studied genes (p&gt;0,05). The presence of a homozygous genotype of the GG polymorphism of the KCNS1 gene (rs734784) was associated with the presence of POP in accordance with the recessive genetic model (GG vs AA+AG; odds ratio (OR) – 3.96 [95% confidence interval (CI): 1.51; 10.37]; p=0.005). The presence of the mutant allele T (TT+CT) in the genotype of the COMT polymorphism (rs4633) reduced the risk of POP compared to the carrier of the CC genotype (OR=0.32 [95% CI: 0.12; 0.83]; p=0.02) in accordance with the dominant genetic model. There was no significant correlation between the development of POP and the carrier of different genotypes and alleles of the COMT (rs6269) and OPRM1 (rs1799971) genes.Conclusions. There is a statistically significant association the polymorphism of the KCNS1 (rs734784) and COMT (rs4633) genes and the development of chronic POP in patients who underwent TKA or THA. Further studies of the genetic predisposition to POP are required on more clinical material.

Evaluation of the Association of COMT Rs4680 Polymorphism with Swimmers' Competitive Performance.

Swimmers’ competitive performance is a result of complicated interactions between physiological, biochemical, physical and psychological factors, all of which are strongly affected by water. Recently, great attention has been paid to the role of genetic factors such as the catechol-O-methyltransferase gene (COMT) influencing motivation, emotions, stress tolerance, self-control, sleep regulation, pain processing and perception, addictive behaviour and neurodegeneration, which may underlie differences in achieving remarkable results in sports competition. Thus, this study was performed to investigate the association between the COMT Val158Met (rs4680) polymorphism and athletic performance in Caucasian swimmers. A total of 225 swimmers (171 short distance (SDS) and 54 long distance swimmers (LDS)) of national or international competitive standard and 379 unrelated sedentary controls were genotyped using real-time polymerase chain reaction (real-time PCR). We found no significant differences in genotypic or allelic distributions between (1) male and female athletes; (2) SDS and LDS; (3) all athletes and sedentary controls (under codominant, dominant, recessive, and overdominant genetic models). No association was found between the COMT rs4680 polymorphism and elite swimming athlete status of the studied population. However, more replication studies are needed.

Polymorphisms of Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 genes in trigeminal neuralgia

SubjectsTrigeminal neuralgia is a neuropathic pain characterized by episodes of severe shock-like pain within the distribution of one or more divisions of the trigeminal nerve. Pain can be influenced by ethnicity, environment, gender, psychological traits, and genetics. Molecules Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 have been involved in mechanisms that underlie pain and neurological conditions. ObjectiveThe aim of this case-control study was to investigate the occurrence of genetic polymorphisms in Nav1.6 sodium channel (SCN8A/rs303810), Brain-derived Neurotrophic Factor (BDNF/rs6265/Val66Met), Catechol-O-methyltransferase (COMT/rs4680/Val158Met), and Guanosine Triphosphate Cyclohydrolase 1 (GCH1/rs8007267) genes in trigeminal neuralgia patients. MethodsNinety-six subjects were divided into two groups: 48 with trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated by visual analog scale and genomic DNA was obtained from oral swabs and analyzed by real-time polymerase chain reaction. ResultsNo association was observed among SCN8A, BDNF, COMT or GCH1 polymorphisms and the presence of trigeminal neuralgia. Genotype distribution and allele frequencies did not correlate to pain severity. ConclusionsAlthough no association of evaluated polymorphisms and trigeminal neuralgia or pain was observed, our data contributes to the knowledge of genetic susceptibility to trigeminal neuralgia, which is very scarce. Further studies may focus on other polymorphisms and mutations, as well as on epigenetics and transcriptional regulation of these genes, in order to clarify or definitively exclude the role of Nav1.6, BDNF, COMT or GCH1 in trigeminal neuralgia susceptibility and pathophysiology.

Factors associated with orthodontic pain.

BackgroundPain experienced at teeth during orthodontic treatment varies largely over time, with the reasons for its interindividual variability being largely unknown: age, sex, clinical activations, psychosocial factors and genetic polymorphisms of candidate genes are putative factors that may account to explain this variability. We aimed to investigate the effect of clinical, demographic, psychological and genetic factors on pain levels experienced during fixed orthodontic treatment.MethodsA convenience sample of 183 patients undergoing full‐fixed orthodontic treatment were recruited. Participant's pain levels were assessed seven times over a three‐day period via a smartphone app. Clinical, demographic and psychological data were collected via questionnaires. This included the Pain Catastrophising Scale (Child version), the Corah Dental Anxiety Scale and the State and Trait Anxiety Inventory. Participants provided a DNA sample either in the form of blood or saliva, which were used for genotyping COMT gene rs6269, rs4680, rs4646310, NR3C1 gene rs2963155 and the HTR2A gene rs9316233.ResultsBond ups had the greatest influence on perceived levels of pain experienced on teeth during orthodontic treatment, accounting for over 20% of total variance in pain response. High‐pain responders had higher scores on pain catastrophising (magnification subscale). Self‐reported pain during fixed orthodontic treatment was not influenced by sex, age, time into treatment, anxiety, nor by polymorphisms of COMT, HTR2A or NR3C1 genes.ConclusionsPain on teeth resulting from orthodontic fixed appliances is stronger during bonds‐up and in patients with high catastrophising scores. Demographics, type of clinical activations and the genetic polymorphisms investigated in this research had little or no impact on perceived pain levels.

Clinical and genetic factors associated with anxiety and depression in breast cancer patients: a cross-sectional study

BackgroundDespite the progress in assessment and treatment of breast cancer, being diagnosed with it or receiving chemotherapy treatment is still conceived as a traumatic experience. Women develop negative thoughts about life and death with detrimental effects on their daily physical functioning/activities, emotional state and overall quality of life. The aim of our study was to evaluate the level of anxiety and depression among breast cancer patients receiving chemotherapy and explore the correlation between these psychological disorders, clinical, sociodemographic and genetic factors.MethodsA cross-sectional study was conducted among breast cancer patients undergoing intravenous chemotherapy at the oncology outpatient unit of Hôtel-Dieu de France hospital (November 2017–June 2019; Ethical approval number: CEHDF1016). All patients gave their written informed consent and completed several validated scales, including the Hospital Anxiety and Depression scale (HADS) for the assessment of anxiety and depression. Sleep quality, insomnia, cognitive function, fatigue and pain were also evaluated. Genotyping for certain gene polymorphisms (CLOCK, PER2, CRY2, OPRM1, ABCB1, COMT, DRD2) was performed using the Lightcycler® (Roche).ResultsA total of 112 women was included. The prevalence of depression was 43.4%, and 56.2% of the patients reported anxiety (based on the HADS classification). Multivariable analysis showed that higher cognitive scores and taking fosaprepitant were significantly associated with lower depression and anxiety scores. Moreover, being married compared to single was also associated with lower depression scores, whereas higher PSQI scores (worse sleep quality) and having the PER2 AA variant genotype compared to GG were significantly associated with higher depression scores. Finally, reporting a more severe insomnia and having the COMT Met/Met genotype were significantly associated with a higher anxiety score.ConclusionsOur study demonstrated a strong relationship between depression scores and cognitive impairment, sleep quality, marital status, fosaprepitant intake, and PER2 polymorphism, while anxiety scores were correlated to cognitive impairment, insomnia severity, fosaprepitant intake, and COMT polymorphism. The association with PER polymorphism was not previously reported. Identification of genetic and clinical risk factors for anxiety and depression would help clinicians implement an individualized management therapy aiming at preventing and alleviating the burden of these symptoms in breast cancer patients, hence improving their overall quality of life.

The role of genetic polymorphisms in executive functioning performance in temporal lobe epilepsy

ObjectiveTo explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE). MethodsNinety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery). ResultsAfter adjustment for general cognitive ability, COMT Val carriers showed poorer performance on semantic verbal fluency and color word interference than non-carriers, and BDNF Met carriers showed poorer performance on phonemic verbal fluency than those without a Met allele. SignificanceResults suggest that COMT and BDNF polymorphisms are associated with performance on several EF measures in patients with TLE, including tasks assessing verbal fluency and response inhibition and account for up to 16% of the variance in test performance. The APOE polymorphism was not significantly associated with any of the executive function measures analyzed.

No association between dopaminergic polymorphisms and response to treatment of binge-eating disorder.

The genetics of binge-eating disorder (BED) is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined if DA genes influence response to behavioral treatment of BED. The primary objective of this study was to examine the ability of DA-associated polymorphisms to predict BED treatment response measured using binge frequency over 12months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity. Women aged 18-64years old were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these 4 polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination - Interview) and body composition (Tanita BC-418) were assessed in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was conducted on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n=72), obesity without BED (n=27), and normal-weight without BED (n=45). There were no significant genotype×time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics. Our study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. Future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as examine their impact on both behavioral and pharmacological-based treatment for BED.

Clinical and Genetic Factors Associated With the Breast Cancer-Related Sleep Disorders: The “CAGE-Sleep” Study–A Cross-Sectional Study

ContextDespite being among the most reported concerns in breast cancer patients, sleep disturbances are still poorly assessed and managed in routine clinical practice. Correctly evaluating these symptoms and understanding the underlying clinical and genetic factors would help medical teams develop an adequate treatment strategy for each patient. Objectives1) To explore the severity of insomnia as well as sleep quality in a sample of Lebanese women with breast cancer undergoing chemotherapy; 2) To examine the correlation between sociodemographic, clinical, psychiatric (anxiety and depression), genetic factors, and alterations in sleep patterns. MethodsA cross-sectional study was carried out using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) (December 2017–June 2019; Ethical reference number: CEHDF1016). All patients gave their written consent and were genotyped for several polymorphisms in CLOCK, CRY2, PER2, COMT, DRD2, OPRM1, and ABCB1 genes using Lightcycler® (Roche). ResultsOur sample included a total of 112 women. Almost half of the patients reported insomnia problems (with 20.5% moderate insomnia and 7.1% severe insomnia). Multivariable analyses taking the PSQI score as the dependent variable, showed that higher depression score and dyslipidemia (yes versus no) were significantly associated with higher PSQI scores (worse sleep quality), whereas having the DRD2 CT genotype versus CC and a higher chemotherapy cycle number were significantly associated with lower PSQI scores (better sleep quality). Depression was also significantly associated with higher ISI scores. When forcing all the genes in each model, the results remained the same except for depression that has been replaced by anxiety in the multivariable analysis. ConclusionOur study confirms the relationship between anxiety/depression, cycle number, dyslipidemia and DRD2 polymorphism with insomnia and highlights the importance of treating all associated factors to improve the overall QOL of patients.

Impact of COMT val158met on tDCS-induced cognitive enhancement in older adults

BackgroundPrevious studies suggest that genetic polymorphisms and aging modulate inter-individual variability in brain stimulation-induced plasticity. However, the relationship between genetic polymorphisms and behavioral modulation through transcranial direct current stimulation (tDCS) in older adults remains poorly understood. ObjectiveLink individual tDCS responsiveness, operationalized as performance difference between tDCS and sham condition, to common genetic polymorphisms in healthy older adults. Methods106 healthy older participants from five tDCS-studies were re-invited to donate blood for genotyping of apoliproprotein E (APOE: ε4 carriers and ε4 non-carriers), catechol-O-methyltransferase (COMT: val/val, val/met, met/met), brain-derived neurotrophic factor (BDNF: val/val, val/met, met/met) and KIdney/BRAin encoding gene (KIBRA: C/C, C/T, T/T). Studies had assessed cognitive performance during tDCS and sham in cross-over designs. We now asked whether the tDCS responsiveness was related to the four genotypes using a linear regression models. ResultsWe found that tDCS responsiveness was significantly associated with COMT polymorphism; i.e., COMT val carriers (compared to met/met) showed higher tDCS responsiveness. No other significant associations emerged. ConclusionUsing data from five brain stimulation studies conducted in our group, we showed that only individual variation of COMT genotypes modulated behavioral response to tDCS. These findings contribute to the understanding of inherent factors that explain inter-individual variability in functional tDCS effects in older adults, and might help to better stratify participants for future clinical trials.

Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson's disease patients: a population-based cohort study.

Levodopa-induced dyskinesia (LID) is an adverse effect that negatively impacts the quality of life of patients with Parkinson's disease (PD). Studies report that genetic variations in the genes of the pharmacogenetic pathway of the levodopa (L-DOPA) might be associated with LID development. The goal of the present study was to investigate a possible influence of functional genetic variants in the DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) genes with LID development. A total of 220 patients with idiopathic PD were enrolled. The genotyping for DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) polymorphisms were performed using Restriction Fragment Length Polymorphism (PCR-RFLP). Univariate and multivariate analyses were performed to assess the association of these polymorphisms and risk factors with LID development. Multivariate Cox regression analysis showed increased risk to LID development for both Levodopa Dose Equivalency (LED) (Hazard ratios (HR) = 1.001; 95% CI 1.00-1.01; p = 0.009) and individuals carrying the COMT L/L genotype (HR = 2.974; 95% CI 1.12-7.83; p = 0.010). Furthermore, when performed a Cox regression analysis adjusted for a total LED, we observed that the genotype COMT L/L had a 3.84-fold increased risk for LID development (HR = 3.841; 95% CI 1.29-11.37; p = 0.012). Our results suggest that before treating LID in PD patients, it is important to take into consideration genetic variant in the COMT gene, since COMT LL genotype may increase the risk for LID development.

VAL158MET catechol O-methyltransferase polymorphism contributes to the development of preeclampsia

ABSTRACT Objectives: Establishment of association between: (a) Val158Met COMT (G1947A) polymorphism and preeclampsia; (b) cytokines gene expression and COMT genotypes. Methods: 50 preeclampsia and 50 healthy pregnant women were enrolled. COMT genotyping was done by PCR/RFLP. TNF-α, IL-1β, and IL-6 mRNA levels were determined by Real-time PCR. Results: Variant (AA) homozygotes carried 3.7-fold increased preeclampsia odds, especially for severe (OR = 9.0, 95%CI (2.09–38.799)) and early forms (OR = 6.6, 95%CI (1.62–26.87)). AA homozygotes with PE had higher TNF-α levels compared to controls (P = 0.012). Conclusions: Val158Met COMT polymorphism increases preeclampsia risk. TNF-α expression and Val158Met COMT polymorphism have concomitant roles in PE pathogenesis.

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial.

To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded. ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs. OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.