STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.
Ontology highlight
ABSTRACT:
SUBMITTER: Crescioli G
PROVIDER: S-EPMC8953705 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.
Crescioli Giada G Lombardi Niccolò N Vagnoli Laura L Bettiol Alessandra A Giunti Laura L Cetica Valentina V Coniglio Maria Luisa ML Provenzano Aldesia A Giglio Sabrina S Bonaiuti Roberto R Mugelli Alessandro A Aricò Maurizio M Messeri Andrea A Vannacci Alfredo A Maggini Valentina V
Pharmaceutics 20220311 3
Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treat ...[more]
Similar Datasets
Project description:Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America.
| S-EPMC4530646 | biostudies-literature
Project description:BackgroundDysregulation of the μ-opioid receptor has been reported in fibromyalgia (FM) and was linked to pain severity. Here, we investigated the effect of the functional genetic polymorphism of the μ-opioid receptor gene (OPRM1) (rs1799971) on symptom severity, pain sensitivity and cerebral pain processing in FM subjects and healthy controls (HC).MethodsSymptom severity and pressure pain sensitivity was assessed in FM subjects (n = 70) and HC (n = 35). Cerebral pain-related activation was assessed by functional magnetic resonance imaging during individually calibrated painful pressure stimuli.ResultsFibromyalgia subjects were more pain sensitive but no significant differences in pain sensitivity or pain ratings were observed between OPRM1 genotypes. A significant difference was found in cerebral pain processing, with carriers of at least one G-allele showing increased activation in posterior cingulate cortex (PCC) extending to precentral gyrus, compared to AA homozygotes. This effect was significant in FM subjects but not in healthy participants, however, between-group comparisons did not yield significant results. Seed-based functional connectivity analysis was performed with the seed based on differences in PCC/precentral gyrus activation between OPRM1 genotypes during evoked pain across groups. G-allele carriers displayed decreased functional connectivity between PCC/precentral gyrus and prefrontal cortex.ConclusionsG-allele carriers showed increased activation in PCC/precentral gyrus but decreased functional connectivity with the frontal control network during pressure stimulation, suggesting different pain modulatory processes between OPRM1 genotypes involving altered fronto-parietal network involvement. Furthermore, our results suggest that the overall effects of the OPRM1 G-allele may be driven by FM subjects.SignificanceWe show that the functional polymorphism of the μ-opioid receptor gene OPRM1 was associated with alterations in the fronto-parietal network as well as with increased activation of posterior cingulum during evoked pain in FM. Thus, the OPRM1 polymorphism affects cerebral processing in brain regions implicated in salience, attention, and the default mode network. This finding is discussed in the light of pain and the opioid system, providing further evidence for a functional role of OPRM1 in cerebral pain processing.
| S-EPMC7821103 | biostudies-literature
Project description:AimTo investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.MethodsThe subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5' nuclease assay.ResultsIn gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.ConclusionContrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interactions on H pylori infection.
| S-EPMC4611576 | biostudies-literature
Project description:Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1α (rs1800587), IL-1β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF-α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF-α rs1799724 as well as alleles of TNF-α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1α, IL-1β, and TNF-α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1α rs1800587 and TNF-α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.
| S-EPMC6455081 | biostudies-literature
Project description:Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.
| S-EPMC9903018 | biostudies-literature
Project description:BACKGROUND: Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the ?-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide ?-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. RESULTS: The plasma ?-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. CONCLUSIONS: Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.
| S-EPMC3602034 | biostudies-literature
Project description:Osteoarthritis (OA) is a multifactorial disease characterized by low-grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case-control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL-4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21-3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17-3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.
| S-EPMC6122495 | biostudies-literature
Project description:BackgroundExaggerated immunological response to repeated inhalation of organic or chemical dusts may lead to Hypersensitivity Pneumonitis among sensitized individuals. Only a few exposed individuals became ill and disease expression pattern is highly variable which suggest that genetic factors may play a role.AimTo investigate interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10 gene polymorphisms in a cohort of pigeon breeder's disease (PBD) patients in comparison with exposed but healthy controls and the association with different patterns of disease.MethodsWe evaluated 40 PBD patients and 70 exposed controls. IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification.ResultsPolymorphism analysis of IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 genotypes and allele frequencies showed no differences between patients and controls. IFN-γ T/T genotype frequency was increased among patients with chronic presentation (RR=2.33, p=0.047) compared with those with acute/subacute presentation. Also, chronic presenting patients had an increased frequency of IFN-γ T allele (50% vs 22.5%, RR=1.76, p=0.011). No differences were found in TNF-α, IL-6, TGF-ß, and IL-10 genotypes neither allelic frequencies between both groups of patients. IL-6 C/C genotype was more frequent in patients who showed chronic evolution (RR=2.54, p=0.017), when comparing with patients with disease resolution.ConclusionIFN-γ T/T and the IL-6 C/C genotypes seem to play a role in HP expression due to avian exposure, as their frequencies are increased in chronic presentations or in those with chronic evolution one year after the initial diagnosis, respectively. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (3): e2020004).
| S-EPMC7690056 | biostudies-literature
Project description:BackgroundTH17/IL-23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal-epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis. However, genetic polymorphisms in the genes of TH17/IL-23 cytokines have not yet been well investigated in BP.MethodsDetection of polymorphisms in IL-17A (rs2275913 and rs3819025), IL-17F (rs2397084 and rs763780), IL-17RA (rs2229151), and IL-23R (rs2201841, rs7530511, rs11209026, and rs10889677) genes were performed following the collection of blood samples and DNA extraction from BP patients and controls. Gene expression of IL-23R was determined by quantitative RT-PCR analysis.ResultsThe prevalence of IL-23R rs7530511 genotypes and alleles, as well as IL-23R rs2201841 alleles, is significantly different between the BP patients and controls. While the minor C-allele of IL-23R rs7530511 is highly present in the patients, the G-allele distribution of IL-23R rs2201841 is significantly more prevalent in the control individuals compared to the BP patients. Genotypes and alleles of other SNPs in IL-17A, IL-17F, and IL-17RA were similarly distributed in patients and controls.ConclusionsNo alteration was found in the gene expression between wild and polymorphic genotypes of IL-23R (rs2201841 and rs7530511) variations, indicating they do not contribute to altering the levels of gene expression in blood. In summary, our data show that the alleles of two SNPs in IL-23R rs2201841 and rs7530511 are associated with BP.
| S-EPMC7767565 | biostudies-literature
Project description:Behçet's disease (BD) is a complex, multisystemic inflammatory disorder of unclear etiology. Single nucleotide polymorphisms in tumor necrosis factor (TNF) and interleukin (IL)-10 genes have been implicated in susceptibility to BD with inconsistent results in several ethnic populations. The aim of this case-control study was to evaluate the association of TNF-α (-308G/A), TNF-β (+252A/G), and IL-10 (-1082G/A, -819C/T, and -592 C/A) polymorphisms with susceptibility of BD in Saudi patients. Molecular genotyping of TNF-α, TNF-β, and IL-10 gene polymorphisms was performed to analyze the alleles and genotypes distribution in 272 Saudi subjects, including BD patients (61) and healthy controls (211). The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher, whereas those of allele G and genotypes GG were significantly lower in BD patients than controls, indicating that A allele and GA genotype are susceptible, while G allele and GG genotype may be refractory to BD. The distribution of frequencies of alleles and genotype of TNF-β (+252A/G) promoter polymorphism was not significantly different between BD patients and healthy controls. Genotypes 1082GG, -819TT, and 592AA of IL-10 polymorphisms are significantly associated with susceptibility risk of BD, while genotypes 1082AA, 1082GA, 819CC, 819CT, 592CC, and 592CA are resistant to BD. This study indicates that TNF-α (-308G/A) and IL-10 (-1082G/A, -819C/T, and -592C/A) polymorphisms are associated with risk of BD susceptibility in Saudi patients. However, larger scale studies in Saudi population as well as in other ethnicities are needed to confirm this association.
| S-EPMC4592046 | biostudies-literature