Analysis of Single Nucleotide Polymorphism A118g Gene Opioid Receptor Mu-1 (OPRM1) In Opioid Analgesic Patients in Indonesia

Introduction: Opioid Receptor Mu-1 or Opioid Receptor Mu-1 (OPRM1) is a prime candidate for pharmacogenetic studies related to the variability of patient response to opioids. This variant is high frequency in Asian populations that is associated with differences in sensitivity and increased need for opioid analgesics in the treatment of pain. Therefore, this study was conducted with the aim of analyzing OPRM1 in patients receiving opioid analgesics in Indonesia, especially in the city of Surabaya. Method: The method used is the Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), where the data collected is recorded and tabulated and then analyzed using SPSS version 20.0. Result: The results showed that the frequency of SNP A118G of the OPRM1 gene was found to be quite high, namely 58 (72.5%) out of a total of 80 subjects. In 40 male subjects, the GG genotype frequency was found to be the highest at 19 (47.5%). While the genotype frequencies of AA, AG and GG were found to be almost comparable in women. Conclusion: Therefore, it can be concluded that the frequency of SNP A118G of the OPRM1 gene was found to be high in the Indonesian population and had a high tendency in the male population, although it was not statistically significant.

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IDENTIFYING THE C677T POLYMORPHISM OF MTHFR GENE BY PCR-RFLP TECHNIQUE

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2011.2.3 ◽

2011 ◽

pp. 28-35

Author(s):

Keyword(s):

Internal Control ◽

Restriction Site ◽

Mthfr Gene ◽

C677t Polymorphism ◽

Mthfr Genotype ◽

Restriction Digest ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Sequencing Technique ◽

Volunteer Group

Background: The C677T polymorphism of MTHFR gene is a risk factor of many diseases. This study is aimed at: (1) Improving a PCR-RFLP process with the own designed primers to identify the C677T polymorphism of MTHFR gene. (2) Evaluating the prevalence of the C677T polymorphism of MTHFR gene in volunteer group. Materials and method: DNA samples was extracted from peripheral blood of 60 volunteers. Designing primers by using FastPCR software, then improving PCR technique. Standardizing the optimal conditions of restriction digest by HinfI. Confirming the results of polymorphism by DNA sequencing technique. Results: We designed successfully primers to amplify fragment of MTHFR gene including C677T polymorphism and an obligatory restriction site of HinfI (as internal control). 0.5 µl of HinfI enzyme (10 U/µl) is enough for restriction digest. The MTHFR genotype frequencies were: 71.67 % (677CC); 25% (677CT); and 3.33 % (677TT). Conclusion: We standardized successfully PCR-RFLP technique to identifying C677T polymorphism of MTHFR gene. Keywords: C677T polymorphism, MTHFR gene, PCR-RFLP

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Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-induced Hyperalgesia

Current Psychopharmacologye ◽

10.2174/2211556009999200628093231 ◽

2020 ◽

Vol 9 (3) ◽

pp. 164-184

Author(s):

Raymond Brewer ◽

Kenneth Blum ◽

Abdalla Bowirrat ◽

Edward J. Modestino ◽

David Baron ◽

...

Keyword(s):

Opioid Analgesic ◽

Opioid Analgesics ◽

Well Being ◽

Deficiency Syndrome ◽

Pain Tolerance ◽

Opioid Agonist ◽

Opioid Agonist Therapy ◽

Analgesic Agents ◽

Opioid Induced Hyperalgesia ◽

Intensive Investigation

Neuroscientists and psychiatrists working in the areas of “pain and addiction” are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This prodopamine regulator may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.

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Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2020-0103 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Lucie Dlouhá ◽

Věra Adámková ◽

Lenka Šedová ◽

Věra Olišarová ◽

Jaroslav A. Hubáček ◽

...

Keyword(s):

Cytochrome P450 ◽

Genetic Polymorphisms ◽

Metabolic Pathways ◽

Cytochromes P450 ◽

Taqman Assay ◽

Cytochrome P450 Enzymes ◽

Roma Population ◽

Czech Population ◽

Genotype Frequencies ◽

Pcr Rflp

AbstractObjectivesCytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.MethodsRoma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.ResultsWe found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.ConclusionsThere were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.

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Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma

Cancers ◽

10.3390/cancers13030529 ◽

2021 ◽

Vol 13 (3) ◽

pp. 529

Author(s):

Silvia Selene Moreno-Guerrero ◽

Arturo Ramírez-Pacheco ◽

Luz María Rocha-Ramírez ◽

Gabriela Hernández-Pliego ◽

Pilar Eguía-Aguilar ◽

...

Keyword(s):

Overall Survival ◽

Genetic Polymorphisms ◽

Poor Prognosis ◽

Serum Levels ◽

Control Group ◽

Mexican Children ◽

Genotype Frequencies ◽

Pcr Rflp ◽

The Impact ◽

Circulating Levels

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

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Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Journal of Psychopharmacology ◽

10.1177/0269881121991992 ◽

2021 ◽

pp. 026988112199199 ◽

Cited By ~ 1

Author(s):

Miriam Sebold ◽

Maria Garbusow ◽

Deniz Cerci ◽

Ke Chen ◽

Christian Sommer ◽

...

Keyword(s):

Alcohol Dependence ◽

Opioid Receptor ◽

Mechanistic Model ◽

Critical Role ◽

Opioid System ◽

Operant Behaviour ◽

Oprm1 Gene ◽

Potential Biomarker ◽

A118g Polymorphism

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

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Evaluation of Frequency of PGC1-α and CKMM Genes Polymorphisms Among Iranian Elite Hockey Athletes

Gene Cell and Tissue ◽

10.5812/gct.117999 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Maryam Valipour ◽

Parvaneh Azarali ◽

Rostam Alizadeh

Keyword(s):

Physical Activity ◽

Environmental Factors ◽

Sample Size ◽

Dna Extraction ◽

Gene Polymorphisms ◽

Small Sample Size ◽

Small Sample ◽

Complex Phenotype ◽

Genotype Frequencies ◽

Pcr Rflp

Background: Physical activity is a complex phenotype influenced by millions of genes and environmental factors. It is well known that physical performance and sports ability are linked to genes variations. Objectives: The aim of this study was to evaluate the frequency of PGC1-α and CKMM gene polymorphisms in elite hockey athletes. Methods: Fifty Iranian elite national hockey athletes and 100 non-athletes participated in this study. To determine the genotypes of PGC1-α and CKMM gene polymorphisms, 2 ml of saliva was sampled and used for DNA extraction. To determine the genotypes, the PCR-RFLP method was employed. After examining the variants, the allele and genotype frequencies of subjects were measured. Results: The results showed no significant differences for the PPARGC1A gene in the percentage of AA, GG, and AG genotypes. Similarly, the percentage of these genotypes of the CKMM gene did not differ significantly between athletes and non-athletes. Conclusions: The results suggest that the gene polymorphisms of PGC1-α and CKMM are the same between the Iranian elite hockey athletes and non-athletes, which may be due to the overlapping effect of other genes and/or the small sample size of the study.

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Healthcare professionals’ perceptions on the use of opioid analgesics for the treatment of cancer-related pain in Cyprus: A mixed-method study

SAGE Open Medicine ◽

10.1177/2050312119841823 ◽

2019 ◽

Vol 7 ◽

pp. 205031211984182

Author(s):

Andreas Charalambous ◽

Marios Zorpas ◽

Constantina Cloconi ◽

Yolanda Kading

Keyword(s):

Pain Relief ◽

Cancer Pain ◽

Mixed Method ◽

Healthcare Professionals ◽

Opioid Analgesic ◽

Opioid Analgesics ◽

Main Barrier ◽

Appropriate Education ◽

Qualitative Phase ◽

Poor Management

Objectives: Pain is considered the most common and debilitating symptom reported by patients affected by cancer, and opioids are at the front line for its effective management. However, the appropriate use of opioids can be limited by healthcare professionals’ perceptions on opioids. Therefore, the aim of this study was to explore their perceptions on the use of opioids medication. Methods: This was a study of sequential mixed-method design conducted in Cyprus. As part of the quantitative phase of the study, the Barriers to Opioid Analgesic Availability Test questionnaire was completed by 73 physicians randomly selected. In the qualitative phase, 28 healthcare professionals working in primary and secondary healthcare centers participated in two focus groups. They were asked to express their perceptions on the use of opioid analgesics for the treatment of cancer-related pain. Data were analyzed according to Colaizzis’ seven-stage phenomenological analysis. Results: The quantitative analysis showed that 69.85% of physicians acknowledge opiophobia as a main barrier to appropriate pain relief but also explicitly for cancer pain which is not adequately managed (45.19%). In terms of opioids availability, physicians stated that moderate to severe problems in opioids availability were mainly caused by their reluctance to prescribe opioids (49.3%) followed by the laws/regulations in place (41.08%). The qualitative analysis yielded the following six main themes: inadequate training of healthcare professionals in the use of opioid analgesics, inadequate patient/caregivers’ awareness of opioid analgesics, opiophobia in healthcare professionals, opiophobia of patients/caregivers, poor management of opioid analgesics by healthcare professionals and patients/caregivers, and ineffective pain relief with opioids. Conclusions: The lack of appropriate education is a significant barrier to opioids use in Cyprus. This is compounded by the attitudes and phobias of both healthcare professionals and the general public. In addition, there are barriers to opioid availability and unsatisfactory cancer pain relief.

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An Effective Intervention: Limiting Opioid Prescribing as a Means of Reducing Opioid Analgesic Misuse, and Overdose Deaths

The Journal of Law Medicine & Ethics ◽

10.1177/1073110520935336 ◽

2020 ◽

Vol 48 (2) ◽

pp. 249-258 ◽

Cited By ~ 1

Author(s):

Brandi C. Fink ◽

Olivier Uyttebrouck ◽

Richard S. Larson

Keyword(s):

Opioid Analgesic ◽

Opioid Analgesics ◽

Fold Increase ◽

Prescribing Patterns ◽

Prescription Opioid ◽

Heroin Use ◽

Overdose Death ◽

Opioid Prescribing ◽

Prescription Opioid Misuse ◽

Overdose Deaths

Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death.

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Study of the Association between microRNA (miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T) Polymorphisms and the Risk of Recurrent Pregnancy Loss in Korean Women

Genes ◽

10.3390/genes11040354 ◽

2020 ◽

Vol 11 (4) ◽

pp. 354 ◽

Cited By ~ 2

Author(s):

Jeong Yong Lee ◽

Jung Oh Kim ◽

Han Sung Park ◽

Chang Soo Ryu ◽

Ji Hyang Kim ◽

...

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Rflp Analysis ◽

Blood Coagulation Disorders ◽

Single Nucleotide Variants ◽

Genotype Combination ◽

Nitrogen Levels ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Immunological Factors

Recurrent pregnancy loss (RPL), which is defined as two pregnancy losses that occur before 20 weeks of gestation, is relatively common, occurring in approximately 1–5% of women. The underlying cause is often unclear, although numerous factors may contribute to RPL, including environmental and immunological factors, blood coagulation disorders, and genetics. In particular, single nucleotide variants have been associated with RPL, including those found in microRNAs (miRNAs). We investigated the association between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125aC>T, and miR-222G>T, and RPL in a cohort consisting of 361 RPL patients and 272 controls. Subjects were genotyped at miRNA loci by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and genotype frequencies were calculated. We then performed allele and genotype combination analyses and measured the association between miRNA polymorphisms and clinical variables in both RPL patients and controls. We detected a statistically significant association between RPL and the miR-25T/miR-32C/miR-125aT/miR-222T allele combination (adjusted odds ratio (AOR), 4.361; 95% confidence interval (CI), 1.496–12.72; P = 0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254–7.588; P = 0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183–7.257; P = 0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084–5.386; P = 0.026) were also associated with RPL. Analysis of variance (ANOVA) revealed that platelet counts and blood urea nitrogen levels were significantly different in RPL patients expressing different miR-125aC>T and miR-25T>C genotypes, respectively (P < 0.05). In addition, creatinine levels were lower in RPL patients expressing the minor alleles miR-25T>C and miR-32C>A. We investigated miRNAs (miR-25, miR-32, miR-125a, miR-222) in RPL patients and healthy controls. Significantly different allele frequencies were detected by ANOVA. We suggest that miRNAs and clinical factors can impact RPL occurrence.

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Relationship Between Opioid Analgesic Prescription and Unemployment in Patients Seeking Acupuncture for Chronic Pain in Urban Primary Care

Pain Medicine ◽

10.1093/pm/pny169 ◽

2018 ◽

Vol 20 (8) ◽

pp. 1528-1533 ◽

Cited By ~ 1

Author(s):

Elizabeth Chuang ◽

Eric N Gil ◽

Qi Gao ◽

Benjamin Kligler ◽

M Diane McKee

Keyword(s):

Primary Care ◽

Low Income ◽

Pain Treatment ◽

Opioid Analgesic ◽

Opioid Analgesics ◽

Baseline Survey ◽

Patient Reported ◽

Nonmalignant Pain ◽

Chronic Nonmalignant Pain ◽

Analgesic Use

Abstract Objective The widespread use of opioid analgesics to treat chronic nonmalignant pain has contributed to the ongoing epidemic of opioid-related morbidity and mortality. Previous studies have also demonstrated a relationship between opioid analgesic use and unemployment due to disability. These studies have been limited to mainly white European and North American populations. The objective of this study is to explore the relationship between opioid analgesic use for chronic nonmalignant pain in an urban, mainly black and Hispanic, low-income population. Design This is a cross-sectional observational study. Setting Subjects were recruited from six urban primary care health centers. Subjects Adults with chronic neck, back, or osteoarthritis pain participating in an acupuncture trial were included. Methods Survey data were collected as a part of the Acupuncture Approaches to Decrease Disparities in Pain Treatment two-arm (AADDOPT-2) comparative effectiveness trial. Participants completed a baseline survey including employment status, opioid analgesic use, the Brief Pain Inventory, the global Patient Reported Outcomes Measurement Information Systems quality of life measure, the Patient Health Questionnaire-9 (PHQ-9), and demographic information. A multivariable logistic regression model was built to examine the association between opioid analgesic use and unemployment. Results Opioid analgesic use was associated with three times the odds of unemployment due to disability while controlling for potential confounders, including depression, pain severity, pain interference, global physical and mental functioning, and demographic characteristics. Conclusions This study adds to the growing body of evidence that opioid analgesics should be used with caution in chronic nonmalignant pain.

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