***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The catechol-O-methyltranferase ( COMT ) is one of the main enzymes that metabolise dopamine in the brain . The Val158Met polymorphism in the COMT gene ( rs4680 ) causes a trimodal distribution of high ( Val/Val ) , intermediate ( Val/Met ) and low ( Met/Met ) enzyme activity . We tested whether the Val158Met polymorphism is a modifier of the age at onset ( AAO ) in Parkinson 's disease ( PD ) . The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin ( 5886 patients with PD and 10 723 healthy controls ) . The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression , with gender , age and cohort origin included in the initial model . The multivariate analysis of the AAO was a mixed linear model , with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as r and om effects . COMT genotype was coded as a quantitative variable , assuming a codominant genetic effect . The distribution of the COMT polymorphism was not significantly different in patients and controls ( p=0.22 ) . The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val ( 57.1±13.9 , p=0.03 ) than the Val/Met ( 57.4±13.9 ) and the Met/Met genotypes ( 58.3±13.5 ) . The difference was greater in men ( 1.9 years between Val/Val and Met/Met , p=0.007 ) than in women ( 0.2 years , p=0.81 ) . Thus , the Val158Met COMT polymorphism  is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism : the Val allele is associated with a younger AAO in men with idiopathic PD Patients with Parkinson 's Disease ( PD ) have a variable response to tolcapone , a catechol-O-methyltransferase ( COMT ) inhibitor . In addition , a subset of patients develop severe diarrhea as a side effect . Two codominant alleles for the COMT gene exist , coding for low and high activity , result ing in low- , medium- , and high-activity genotypes . This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone .  To investigate the relationship between COMT polymorphism and clinical response , 24 patients who completed tolcapone clinical trials provided blood sample s for COMT genotype analysis . Change in levodopa dose and United Parkinson Disease Rating Scale ( UPDRS ) Part III ( motor subscale ) were analyzed at baseline , at 1–2 weeks , and 6 months after initiation of tolcapone . Genotype analysis was performed on seven patients who had diarrhea as a side effect . There was no significant correlation between genotype and improvement in UPDRS score ( p = 0.29 ) according to a linear models approach that adjusted for the subject 's severity of PD , tolcapone dose ( either 100 or 200 mg three times daily ) and initial differences in baseline scores . No significant difference was seen in change in daily levodopa intake and genotype . There was also no relation between diarrhea and COMT genotype . These results indicate that , in the treatment of Parkinson 's disease , COMT genotype is not a major contributor to the clinical response to tolcapone Background A polymorphism ( G to A transition ) in intron 13 of the mitochondrial enzyme monoamine oxidase B ( MAOB ) gene may modify , alone or by interacting with the catechol-O-methyltransferase ( COMTLL ) genotype ( low enzymatic activity ) , the risk of idiopathic PD . Also , the association between never smoking and PD risk may be present only in people with the MAOB G allele . Methods The authors studied two ongoing prospect i ve cohorts — the Nurses ’ Health Study ( 121,700 women aged 30 to 55 in 1976 ) and the Health Professionals ’ Follow-up Study ( 51,529 men aged 40 to 75 in 1986 ) . They identified new PD cases through 1996 , selected r and om control subjects matched on age and study cohort , and obtained DNA sample s from blood or buccal smears from 85 % of the eligible cases and 84 % of the control subjects . They included genotypes from 214 cases and 449 control subjects , all Caucasian . Results The odds ratio of PD was 1.2 ( 95 % CI 0.9 , 1.7 ) for MAOB genotypes G/GG/GA compared with genotypes A/AA , and 1.1 ( 0.7 , 1.8 ) for COMT genotypes LL compared with HH . The odds ratio ( 95 % CI ) was 1.7 ( 0.7 , 3.9 ) for those with MAOB G/GG and COMTLL genotypes compared with those with MAOB A/AA and COMTHH . There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes . Conclusion The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD , either by itself or by interacting with smoking A single nucleotide polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase ( COMT ) gene encodes the high and low activity forms of the enzyme . We investigated COMT genotypes of 73 Korean patients with Parkinson 's disease ( PD ) , 29 with multiple system atrophy ( MSA ) , and 49 controls , and analyzed the response to levodopa challenge  in the PD patients . We found no significant difference in the distribution of the COMT genotypes among the three groups . The frequencies of the G- and A-alleles in the total population were 75 and 25 % , respectively . The levodopa response was determined by a single oral levodopa challenge test with Sinemet ( 25/250 mg ) in the patients with PD . The motor response evaluated by the time to peak response , the duration and magnitude of the response in the motor part of the Unified Parkinson 's Disease Rating Scale ; tapping or walking times showed no significant difference between the genotypes . Thus , pharmacokinetic or pharmacodynamic factors other than the investigated genetic variant of the COMT enzyme seem to determine the response to levodopa in PD The role of genetic factors in cognitive decline  associated with Parkinson 's disease ( PD ) is unclear . We examined whether variations in apolipoprotein E ( APOE ) , microtubule-associated protein tau ( MAPT ) , or catechol-O-methytransferase ( COMT ) genotypes are associated with cognitive decline in PD . We performed a prospect i ve cohort study of 212 patients with a clinical diagnosis of PD . The primary outcome was change in Mattis Dementia Rating Scale version 2 score . Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time . The ε4 allele of APOE was associated with more rapid decline ( loss of 2.9 ; 95 % confidence interval [ CI ] : 1.7 - 4.1 ) of more points per year ; P < 0.001 ) in total score and an increased risk of a ≥ 10 point drop during the follow-up period ( hazard ratio , 2.8 ; 95 % CI : 1.4 - 5.4 ; P = 0.003 ) . MAPT haplotype and COMT genotype were associated with measures of memory and attention , respectively , over the entire follow-up period , but not with the overall rate of cognitive decline . These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages . Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD , supporting the idea of a component of shared etiology between PD dementia and Alzheimer 's disease . Clinical ly , these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients Pyridoxal‐5‐phosphate , the biological active form of pyridoxine , is a cofactor for dopa‐decarboxylase ( DDC ) enzyme . Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain . However , this effect can be negated in the presence of a DDC inhibitor , which potentiates plasma levodopa level . A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase ( COMT ) gene encodes the high ( COMTH ) and low activity ( COMTL ) forms of the enzyme . In this study , we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson 's disease ( PD ) patients . PD patients who were on stable and optimized dose of levodopa were included in this study .  Their mean motor and activities of living score improved after high dose pyridoxine ( P = 0.09 , P = 0.04 ) , and worsened after a washout period ( P = 0.005 , P = 0.001 ) . Using a multivariate model , the presence of the COMTL allele predicted response to pyridoxine , with the best outcome observed in COMTL/L homozygotes . Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy . © 2005 Wiley‐Liss , Catechol-O-methyltransferase ( COMT ) is an enzyme that inactivates catecholamines such as adrenaline , noradrenaline , dopamine , and levodopa . Recently an amino acid change ( Val-108-Met ) of the COMT protein was found to determine high and low activity alleles of the COMT gene . We genotyped 109 Japanese patients with Parkinson 's disease ( PD ) and 153 controls by using polymerase chain reaction ( PCR ) amplification and digestion by the restriction enzyme NlaIII . The frequency of low activity allele in the controls was 0.29 , which was significantly different from that reported in Caucasians ( 0.50 ) . When comparison was made between patients with PD and controls , homozygosity for the low activity allele was significantly more common among the patients than among the controls ( P = 0.017 ; odds ratio , 2.8 , 95 % CI 1.2 - 6.5 ) , suggesting that homozygosity for the low activity allele may increase susceptibility to PD We explored the potential effect of catechol-O-methyltransferase ( COMT ) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a st and ard oral dose of levodopa in patients with Parkinson 's disease ( PD ) . We prospect ively collected blood sample s for COMT genotyping from a population of 104 PD patients . Each patient was examined by a st and ard oral levodopa/benserazide test , based on simultaneous serial measurements of plasma levodopa concentrations , finger-tapping motor effects and dyskinesia ratings , up to 4 hours after dosing . The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration , plasma elimination half-life , and the area under the plasma concentration-time curve . The main outcome levodopa pharmacodynamic variables were latency , duration , and magnitude of the motor effect elicited by the levodopa test dose , the area under the tapping effect-time curve , and the presence of dyskinesias . Nineteen patients ( 18 % ) harbored the low-activity homozygous COMT genotype ( A/A ) , 63 patients ( 61 % ) carried the intermediate-activity heterozygous COMT genotype ( A/G ) and 22 patients ( 21 % ) had the high-activity homozygous COMT genotype ( G/G ) . The three groups were comparable for vital and clinical characteristics . No significant difference was found in levodopa main pharmacokinetic-pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients . We failed to identify clinical ly relevant levodopa pharmacokinetic-pharmacodynamic response patterns associated with the COMT polymorphism in PD patients Objective To investigate the relationship between the catechol-O-methyltransferase ( COMT ) genotype and the therapeutic efficacy of entacapone . Methods The efficacy of 2 months of entacapone treatment in 65 patients with PD with end-of-dose deterioration was studied . The efficacy of entacapone was assessed using the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) score , the daily levodopa dosage , and the patients ’ diary card . Results Thirty-six patients ( 55.4 % ) had a high-activity COMT gene ( COMTHH ) , 22 ( 33.8 % ) had an intermediate-activity COMT gene ( COMTHL ) , and 7 patients ( 10.8 % ) had a low-activity COMT gene ( COMTLL ) . Two months of entacapone treatment result ed in a significant increase in “ on ” time , a reduction in “ off ” time , and a reduction in the total UPDRS score , but these results were independent of the COMT genotype 
    Output:
    
COMT genotypes could be related with a modest modification in the age at onset of PD , but its possible genotypes in excessive daytime somnolence , impulse control disorders , cognitive impairment , and neuropharmacological or neurochemical variables are unclear .
The results of the meta- analysis suggest that the COMT rs4680 polymorphism is not a major determinant of either the risk for PD or clinical , neuropharmacological and neurochemical features of PD .
Data on other COMT polymorphisms are scarce but do not suggest association with PD