Influence of Catechol-O-Methyltransferase Gene Polymorphism on the Correlation between Alexithymia and Hypervigilance to Pain

The psychological characteristic of having difficulty expressing emotions, known as alexithymia, is associated with hypervigilance to pain and is considered one of the risk factors for chronic pain. The correlation between alexithymia and hypervigilance to pain can be observed even in healthy individuals. However, the factors influencing this correlation remain unknown. We explored the dopamine system, which is known to be involved in emotion and pain. The dopamine-degrading enzyme catechol-O-methyltransferase (COMT) has a genetic polymorphism known to influence dopamine metabolism in the prefrontal cortex. COMT polymorphism reportedly affects various aspects of pain and increases pain sensitivity in Met allele carriers. Therefore, we investigated whether the correlation between alexithymia and hypervigilance to pain is influenced by COMT polymorphism in healthy individuals. The results revealed a significant positive correlation between the “difficulty describing feelings” of the 20-item Toronto Alexithymia Scale and the “attention to changes in pain” of the pain vigilance and awareness questionnaire in COMT Met carriers but not in Val/Val individuals. This finding suggests that the correlation between alexithymia and hypervigilance to pain is influenced by COMT polymorphism.

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>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.

Association of COMT Polymorphism and Academic Achievement among Female Undergraduate Students

Academic achievement may be influenced by catechol-O-methyltransferase (COMT) polymorphism. A common functional polymorphism of COMT, the rs4680 is consistently being involved in the modulation of dopaminergic pathway and prefrontal cortex function which may predominantly affect cognitive functions. A total of 197 female participants were recruited in this study. The score of student’s grade point average (GPA) from the latest previous semester was used as the measurement of academic achievement. The COMT polymorphism was genotyped using tetra primer allele specific polymerase chain reaction. The findings indicated that there were 8 (4.1 %), 72 (36.5 %), and 117 (59.4 %) participants harbouring Met/Met, Met/Val, and Val/Val genotype for COMT polymorphism respectively. All the genotype distributions of COMT polymorphism were consistent with Hardy-Weinberg equilibrium (χ2 = 0.495, p > 0.05). The one-way analysis of variance (ANOVA) result demonstrated that participants bearing Met/Met genotype had a better achievement in GPA as compared to the other COMT genotypes (p = 0.001). These findings support evidence that the affective role of COMT polymorphism might overwhelm cognitive abilities in measures of academic achievement like GPA.

Catechol-O-methyltransferase and dopamine receptor D4 gene variants: Possible association with substance abuse in Bangladeshi male

Genetic risk of substance abuse is encoded mainly by central neurochemical pathways(mostly dopaminergic system) related to reinforcement and reward. In this study a functionalpolymorphism in Catechol-O-methyltransferase (COMT) (Val158Met) and the Dopamine receptor D4 gene (DRD4) (120 bp tandem duplication) has been studied in substance abused subjects. The study was carried out with 183 substance abused subjects and 175 healthy persons with no history of substance abuse. DNA was extracted and polymorphisms were analyzed using allele-specific PCR. The impact of these two polymorphisms was also analyzed on addictive characteristics (age of starting abuse, a pattern of drug habit, and period of addiction). It was found that only the heterozygous variant of COMT polymorphism (Val/Met) (p<0.05, OR = 1.66, 95% CI = 1.044–2.658) and both homozygous (p<0.05, OR = 0.43, 95% CI = 0.193–0.937) and heterozygous (p<0.05, OR = 0.37, 95% CI = 0.172–0.826) derived variants of DRD4 120 bp tandem duplication were significantly associated with risk of substance abuse compared to controls. In case of association of these polymorphisms with an age of onset, no significant difference was found among three different genotypic groups of COMT polymorphism. Whereas, the homozygous derived variant (240 bp/240 bp) of DRD4 gene was found to have a later age of onset (20.5±0.8) for substance abuse compared to heterozygous (120 bp/240 bp) (19.1±0.8) and wild type homozygous variant (120 bp/120 bp) (16.0±0.5), which was statistically significant (p<0.05). Again, in the case of the pattern of drug habit, the frequency of the Val/Val genotype is higher in polysubstance abused (>2 drugs) subjects (p<0.05) compared to the heterozygous Val/Met containing variants. An association of period of addiction was analyzed with an individual type of substance abuse and found that heroin abused subjects have a significantly higher period of addiction (11.6±1.0) compared to other abusers (p<0.01). Further, it was found that Met/Met containing variants of COMT polymorphism has a more extended period of addiction than other genetic variants in heroin abused subjects. These results indicate that genetic variability may influence the susceptibility to the risk of substance abuse and addictive characteristics.

Dopamine-Related Genotype Predicts Trajectories of Gait Reserve in Older Adults

The capacity to increase one’s gait speed is critical for maintaining safe community ambulation. There is limited work on the longitudinal changes in this capacity and its predictors. Because lower dopamine is associated with lower task adaptation and motivation, we hypothesized that lower dopamine would predict more decline in rapid gait speed. Catechol-O-methyltransferase (COMT) polymorphism and at least 3 repeated rapid and usual pace gait speed assessments were obtained over 10 years in 1,261 older adults (mean age=75.2, 867 White, 659 women). Linear mixed models computed person-specific rapid and usual pace gait speed trajectories. Regression models adjusted for usual gait trajectory tested whether COMT predicted rapid gait trajectory; covariates included, demographic, psychological, cognitive, and physical factors. Val/Val carriers (lower dopamine) declined more in rapid gait compared to Met/Met carriers (higher dopamine; adjusted b=-.002, SE=.001, p=.042). Modifying dopamine may positively influence the ability to maintain rapid gait over time.