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1.
We conducted a meta-analysis of studies examining the association between the Val158Met COMT polymorphism and violence against others in schizophrenia. A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and the National Criminal Justice Reference Service and identified 15 studies comprising 2,370 individuals with schizophrenia for inclusion. Bivariate analyses of study sensitivities and specificities were conducted. This methodology allowed for the calculation of pooled diagnostic odds ratios (DOR). Evidence of a significant association between the presence of a Met allele and violence was found such that men''s violence risk increased by approximately 50% for those with at least one Met allele compared with homozygous Val individuals (DOR = 1.45; 95% CI = 1.05–2.00; z = 2.37, p = 0.02). No significant association between the presence of a Met allele and violence was found for women or when outcome was restricted to homicide. We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.  相似文献   

2.
OBJECTIVES: About 25,000 serious methamphetamine abusers live in the Czech Republic among the total population of 10 million. Dependence on methamphetamine is markedly related to the brain neurotransmitter dopamine, metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country. Methods: One hundred and twenty-three subjects dependent on methamphetamine (women N=44), parents of sixty-seven dependent individuals, and four hundred healthy controls (women N=250) were involved into the study. We performed a population-based as well as family-based genetic association studies. Results: We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence using the population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED program, Version 3.1.4, respectively). We found a trend toward a statistically significant difference between the Val allele carriers and Met/Met homozygotes in the frequence of psychotic symptoms induced by methamphetamine (more frequent in Val carriers; p=0.062; Chi-Square Test). Conclusion: Further research involving haplotype analysis and other dopamine-related genetic polymorphisms in large populations is needed. More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence.  相似文献   

3.
Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.  相似文献   

4.

Introduction

Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger’s Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val.

Conclusions

Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain’s reward circuits.  相似文献   

5.
The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.  相似文献   

6.

Background

“Imaging genetics” studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS).

Methodology/Principal Findings

Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls.

Conclusions/Significance

These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging.  相似文献   

7.
The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype × gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial superior frontal gyrus (mSFG) was found only in male Val/Val subjects. The rsFC analysis revealed that both the PCC and mSFG were functionally correlated with brain regions of the default mode network (DMN). Both of these regions showed decreased rsFCs with different parts of the frontopolar cortex of the DMN in Val/Val individuals than Met carriers. Our findings suggest that the COMT Val158Met polymorphism modulates both the structure and functional connectivity within the DMN and that gender interactions should be considered in studies of the effect of this genetic variant, especially those involving prefrontal morphology.  相似文献   

8.
Goel N  Banks S  Lin L  Mignot E  Dinges DF 《PloS one》2011,6(12):e29283

Background

The COMT Val158Met polymorphism modulates cortical dopaminergic catabolism, and predicts individual differences in prefrontal executive functioning in healthy adults and schizophrenic patients, and associates with EEG differences during sleep loss. We assessed whether the COMT Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis.

Methodology/Principal Findings

20 Met/Met, 64 Val/Met, and 45 Val/Val subjects participated in a protocol of two baseline 10h time in bed (TIB) nights followed by five consecutive 4 h TIB nights. Met/Met subjects showed differentially steeper declines in non-REM EEG slow-wave energy (SWE)—the putative homeostatic marker of sleep drive—during PSD, despite comparable baseline SWE declines. Val/Val subjects showed differentially smaller increases in slow-wave sleep and smaller reductions in stage 2 sleep during PSD, and had more stage 1 sleep across nights and a shorter baseline REM sleep latency. The genotypes, however, did not differ in performance across various executive function and cognitive tasks and showed comparable increases in subjective and physiological sleepiness in response to chronic sleep loss. Met/Met genotypic and Met allelic frequencies were higher in whites than African Americans.

Conclusions/Significance

The COMT Val158Met polymorphism may be a genetic biomarker for predicting individual differences in sleep physiology—but not in cognitive and executive functioning—resulting from sleep loss in a healthy, racially-diverse adult population of men and women. Beyond healthy sleepers, our results may also provide insight for predicting sleep loss responses in patients with schizophrenia and other psychiatric disorders, since these groups repeatedly experience chronically-curtailed sleep and demonstrate COMT-related treatment responses and risk factors for symptom exacerbation.  相似文献   

9.
In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.  相似文献   

10.
11.
Extracellular superoxide dismutase (EC-SOD) is the main SOD isoform in the arterial wall contributing to cardiovascular defense against oxidative stress by removing the superoxide anion. In our study, the Thr40Ala and Arg213Gly polymorphic variants of the EC-SOD gene (SOD ( 3 )) were investigated for associations with atherosclerosis and other related factors in 144 subjects with significant atheroma (having one, two, or three major coronary arteries with >50% obstruction, and/or peripheral artery lesions, and/or carotid artery stenosis demonstrated by angiography and echography) and in 150 subjects with no significant atheroma. For the Arg213Gly polymorphism, only five heterozygous subjects were found. Although the difference in the genotype distribution for the Thr40Ala polymorphism was not statistically significant between patients with atheroma (AA 49.3%, AG 34.7%, GG 16.0%) and those without significant atheroma (AA 41.3%, AG 43.3%, GG 15.3%), there was an association of the Thr40 allele with diabetes (P = 0.03) and hypertension (P = 0.04).  相似文献   

12.

Background

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

Methods

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

Results

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

Conclusion

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

13.
Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in women of reproductive age, is associated with negative moods. Whether the menstrual pain and negative moods have a genetic basis remains unknown. Brain-derived neurotrophic factor (BDNF) plays a key role in the production of central sensitization and contributes to chronic pain conditions. BDNF has also been implicated in stress-related mood disorders. We screened and genotyped the BDNF Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20–30 years old) and 101 age-matched healthy female controls. We found that there was a significantly higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger association with PDM compared with Val carrier status. Subsequent behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory dimension) and a more anxious mood than the Val carrier PDMs during the menstrual phase. Although preliminary, our study suggests that the BDNF Val66Met polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met homozygosity may be associated with an increased risk of PDM. Our data also suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote an ethnic attribution. The presentation of our findings calls for further genetic and neuroscientific investigations of PDM.  相似文献   

14.
We examined the effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism (rs4680), on brain structure in a subset (N = 82) of general population members of the Northern Finland 1966 Birth Cohort, selected through a randomization procedure, aged 33-35. Optimised voxel-based morphometry was used to produce grey matter maps from each subject's high resolution T1 weighted brain magnetic resonance images, which were subsequently entered into a general linear model with COMT genotype as defined by Met allele loading, gender and genotype by gender interaction as independent variables. Additional analyses were carried out on grey matter volumes within the dorsal lateral pre-frontal cortex (DLPFC) to examine effects on overall DLPFC volume and also using the DLPFC as a mask for voxelwise analyses, as this is an area previously reported as associated with Met allele loading. We failed to find any statistically significant association with grey matter volume and Met allele loading in the COMT gene or interaction affects between COMT and gender in either the whole brain voxel-wise analysis or in the area of the DLPFC.  相似文献   

15.
The COMT Val158Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val158Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non‐invasive DNA analysis. We identified the human COMT Val158Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val158Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non‐human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter‐individual variation in aggression.  相似文献   

16.
Research shows that self-control is resource limited and there is a gradual weakening in consecutive self-control task performance akin to muscle fatigue. A body of evidence suggests that the resource is glucose and consuming glucose reduces this effect. This study examined the effect of glucose on performance in the antisaccade task - which requires self-control through generating a voluntary eye movement away from a target - following self-control exertion in the Stroop task. The effects of motivation and individual differences in self-control were also explored. In a double-blind design, 67 young healthy adults received a 25g glucose or inert placebo drink. Glucose did not enhance antisaccade performance following self-control exertion in the Stroop task. Motivation however, predicted performance on the antisaccade task; more specifically high motivation ameliorated performance decrements observed after initial self-control exertion. In addition, individuals with high levels of self-control performed better on certain aspects of the antisaccade task after administration of a glucose drink. The results of this study suggest that the antisaccade task might be a powerful paradigm, which could be used as a more objective measure of self-control. Moreover, the results indicate that level of motivation and individual differences in self-control should be taken into account when investigating deficiencies in self-control following prior exertion.  相似文献   

17.
The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case–control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.  相似文献   

18.
He XF  Wei W  Li SX  Su J  Zhang Y  Ye XH  Liu Y  Wang W 《Molecular biology reports》2012,39(6):6811-6823
Many studies have reported the role of COMT Val158Met with breast cancer risk, but the results remained controversial. In addition, previous meta-analysis on COMT Val158Met showed conflicting results. Hence, we performed a meta-analysis to investigate the association between breast cancer and COMT Val158Met (30,199 cases and 38,922 controls) in different inheritance models. When all the eligible studies were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and COMT Val158Met polymorphism in any genetic model (dominant model: odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94–1.04, P value of heterogeneity test [P h] = 0.009, I 2 = 36.9%; recessive model: OR = 0.97, 95% CI = 0.92–1.02, P h = 0.044, I 2 = 28.6%; additive model: OR = 0.98, 95% CI = 0.91–1.05, P h = 0.004, I 2 = 40.4%). However, significant between-study heterogeneity was detected in any genetic model. Hence, we performed the stratified analysis according to ethnicity, source of controls, menopausal status, and family history. In the stratified analysis by ethnicity significantly decreased breast cancer risk was observed in Caucasian population (recessive model: OR = 0.96, 95% CI = 0.92–1.00, P h = 0.419, I 2 = 3.1%). In conclusion, this meta-analysis indicates that COMT Val158Met polymorphism may be associated with decreased breast cancer risk in Caucasian population. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on COMT Val158Met polymorphisms and breast cancer risk.  相似文献   

19.
In Drosophila melanogaster, natural genetic variation in the foraging gene affects the foraging behaviour of larval and adult flies, larval reward learning, adult visual learning, and adult aversive training tasks. Sitters (for s) are more sedentary and aggregate within food patches whereas rovers (forR) have greater movement within and between food patches, suggesting that these natural variants are likely to experience different social environments. We hypothesized that social context would differentially influence rover and sitter behaviour in a cognitive task. We measured adult rover and sitter performance in a classical olfactory training test in groups and alone. All flies were reared in groups, but fly training and testing were done alone and in groups. Sitters trained and tested in a group had significantly higher learning performances compared to sitters trained and tested alone. Rovers performed similarly when trained and tested alone and in a group. In other words, rovers learning ability is independent of group training and testing. This suggests that sitters may be more sensitive to the social context than rovers. These differences in learning performance can be altered by pharmacological manipulations of PKG activity levels, the foraging (for) gene''s gene product. Learning and memory is also affected by the type of social interaction (being in a group of the same strain or in a group of a different strain) in rovers, but not in sitters. These results suggest that for mediates social learning and memory in D. melanogaster.  相似文献   

20.
Russian Journal of Genetics - The aim of this study was to investigate the associations between the polymorphic loci in the JAK/STAT signaling pathway and the aging processes and longevity in the...  相似文献   

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