BMC Anesthesiol. 2023 Feb 16;23(1):55. doi: 10.1186/s12871-023-02018-y.

ABSTRACT

BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient.

METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters.

RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes.

CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result.

TRIAL REGISTRATION: NCT02750163.

PMID:36797680 | DOI:10.1186/s12871-023-02018-y

Eur J Hum Genet. 2023 Feb 16. doi: 10.1038/s41431-023-01315-x. Online ahead of print.

NO ABSTRACT

PMID:36797469 | DOI:10.1038/s41431-023-01315-x

J Biol Chem. 2023 Feb 14:103026. doi: 10.1016/j.jbc.2023.103026. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a typical T cell-mediated chronic liver disease with a higher incidence in females. However, the molecular mechanism for the female predisposition is poorly understood. Estrogen sulfotransferase (Est) is a conjugating enzyme best known for its function in sulfonating and deactivating estrogens. The goal of this study is to investigate whether and how Est plays a role in the higher incidence of AIH in females. Concanavalin A (ConA) was used to induce T cell-mediated hepatitis in female C57BL/6J mice. We first showed that Est was highly induced in the liver of ConA-treated mice. Systemic or hepatocyte-specific ablation of Est, or pharmacological inhibition of Est protected female mice from ConA-induced hepatitis regardless of ovariectomy, suggesting the effect of Est inhibition was estrogen independent. In contrast, we found that hepatocyte-specific transgenic reconstitution of Est in the whole-body Est knockout (EstKO) mice abolished the protective phenotype. Upon the ConA challenge, EstKO mice exhibited a more robust inflammatory response with elevated production of pro-inflammatory cytokines and changed liver infiltration of immune cells. Mechanistically, we determined that ablation of Est led to the hepatic induction of lipocalin 2 (Lcn2), whereas ablation of Lcn2 abolished the protective phenotype of EstKO females. Our findings demonstrate that hepatocyte Est is required for the sensitivity of female mice to ConA-induced and T -cell- mediated hepatitis in an estrogen-independent manner. Est ablation may have protected female mice from ConA-induced hepatitis by upregulating Lcn2. Pharmacological inhibition of Est might be a potential strategy for the treatment of AIH.

PMID:36796516 | DOI:10.1016/j.jbc.2023.103026

Expert Opin Drug Saf. 2023 Feb 15. doi: 10.1080/14740338.2023.2181337. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are of great concern in clinical practice. Pharmacogenetics can identify individuals and groups at increased risk of developing ADRs, enabling treatment adjustments to improve outcomes. The study aimed to determine the prevalence of ADRs related to drugs with pharmacogenetic evidence level 1A in a public hospital in Southern Brazil.

RESEARCH DESIGN AND METHODS: ADR information was collected from the pharmaceutical registries from 2017 to 2019. Drugs that have pharmacogenetic evidence level 1A were selected. Public genomic databases were used to estimate the genotypes/phenotypes frequency.

RESULTS: During the period, 585 ADRs were spontaneously notified. Most were moderate (76.3%), whereas severe reactions accounted for 33.8%. Additionally, 109 ADRs caused by 41 drugs presented pharmacogenetic evidence level 1A, representing 18.6% of all notified reactions. Depending on the drug-gene pair, up to 35% of individuals from Southern Brazil could be at risk of developing ADRs.

CONCLUSIONS: Relevant amount of ADRs were related to drugs with pharmacogenetic recommendations on drug labels and/or guidelines. Genetic information could guide and improve clinical outcomes, decreasing ADR incidence and reducing treatment costs.

PMID:36794346 | DOI:10.1080/14740338.2023.2181337

Cardiovasc Res. 2023 Feb 15:cvad025. doi: 10.1093/cvr/cvad025. Online ahead of print.

NO ABSTRACT

PMID:36790900 | DOI:10.1093/cvr/cvad025

J Clin Pharmacol. 2023 Feb 15. doi: 10.1002/jcph.2213. Online ahead of print.

NO ABSTRACT

PMID:36790080 | DOI:10.1002/jcph.2213

Nicotine Tob Res. 2023 Feb 15:ntac268. doi: 10.1093/ntr/ntac268. Online ahead of print.

ABSTRACT

BACKGROUND: Genetic variation in CYP2A6, the major nicotine metabolizing enzyme, is associated with nicotine dependence and smoking cessation. Nicotine dependence severity also predicts smoking cessation. Our goals were to determine how CYP2A6 variation and nicotine dependence alter smoking cessation, and whether dependence could refine CYP2A6-based treatment recommendations.

METHODS: Adult smokers treated for 12 weeks with placebo, nicotine patch, or varenicline (NCT01314001) were grouped as CYP2A6 normal (n=567) or slow (n=432) nicotine metabolizers based on a CYP2A6 weighted genetic risk score. FTND scores were measured at baseline and biochemically-verified smoking cessation was assessed at end-of-treatment.

RESULTS: Dependence neither mediated nor moderated an association between CYP2A6 variation and smoking cessation overall, within any treatment arm, or after stratifying by ancestry (n=591 European, n=408 African ancestry) or sex (n=444 women, n=555 men). In within-treatment analyses, the mediation effect odds ratio (OR) ranged from 0.95-1.00 and the bias-corrected 95% confidence interval contained 1. Moderation (i.e., interaction) effect ORs ranged from 0.88-1.61 (P=0.397-0.828). For CYP2A6 normal metabolizers, quit rates on varenicline were similar for those with high (41.1%) and low (43.4%) dependence, while quit rates were lower for those with high vs. low dependence on both patch (16.5 vs. 29.7%) and placebo (8.9 vs. 18.5%). CYP2A6 slow metabolizers with high vs. low dependence had lower quit rates in all three treatment arms.

CONCLUSIONS: While nicotine dependence severity neither mediated nor moderated CYP2A6 associations with smoking cessation, incorporating information on dependence may optimize the choice of smoking cessation treatment aid in CYP2A6 normal and slow metabolizers.

IMPLICATIONS: Variation in CYP2A6 and nicotine dependence severity alter smoking cessation success. Our findings suggest that while nicotine dependence severity is unlikely to mediate or moderate CYP2A6 associations with cessation, incorporating patient information on both CYP2A6 and nicotine dependence severity may lead to improved smoking cessation strategies.

PMID:36789481 | DOI:10.1093/ntr/ntac268

Ecol Evol. 2023 Feb 7;13(2):e9773. doi: 10.1002/ece3.9773. eCollection 2023 Feb.

ABSTRACT

Species interactions drive diverse evolutionary outcomes. Speciation by cascade reinforcement represents one example of how species interactions can contribute to the proliferation of species. This process occurs when the divergence of mating traits in response to selection against interspecific hybridization incidentally leads to reproductive isolation among populations of the same species. Here, we investigated the population genetic outcomes of cascade reinforcement in North American chorus frogs (Hylidae: Pseudacris). Specifically, we estimated the frequency of hybridization among three taxa, assessed genetic structure within the focal species, P. feriarum, and ascertained the directionality of gene flow within P. feriarum across replicated contact zones via coalescent modeling. Through field observations and preliminary experimental crosses, we assessed whether hybridization is possible under natural and laboratory conditions. We found that hybridization occurs among P. feriarum and two conspecifics at a low rate in multiple contact zones, and that gene flow within the former species is unidirectional from allopatry into sympatry with these other species in three of four contact zones studied. We found evidence of substantial genetic structuring within P. feriarum including a divergent western allopatric cluster, a behaviorally-distinct sympatric South Carolina cluster, and several genetically-overlapping clusters from the remainder of the distribution. Furthermore, we found sub-structuring between reinforced and nonreinforced populations in the two most intensely-sampled contact zones. Our literature review indicated that P. feriarum hybridizes with at least five heterospecifics at the periphery of its range providing a mechanism for further intraspecific diversification. This work strengthens the evidence for cascade reinforcement in this clade, revealing the geographic and genetic landscape upon which this process can contribute to the proliferation of species.

PMID:36789346 | PMC:PMC9905665 | DOI:10.1002/ece3.9773

Pharmacogenomics. 2023 Feb 14. doi: 10.2217/pgs-2022-0194. Online ahead of print.

ABSTRACT

The Indo-Swiss symposium on pharmacogenomic strategies for the implementation of personalized medicine was conducted as part of the Jawaharlal Institute of Postgraduate Medical Education and Research Integrated Pharmacogenomics Program in Puducherry, India, on 19 November 2022. The symposium was conducted in hybrid mode. The theme of symposium was the impact of pharmacogenomics on the achievement of personalized medicine/precision medicine in the clinical setting. The symposium sought to promote interaction among the participants to initiate future collaborative research projects. The symposium also served as a platform for young researchers to present their research findings as posters to the audience.

PMID:36786192 | DOI:10.2217/pgs-2022-0194

Med Rev (Berl). 2022 Nov 30;2(6):611-624. doi: 10.1515/mr-2022-0032. eCollection 2022 Dec.

ABSTRACT

Xenobiotic receptors are traditionally defined as xenobiotic chemical-sensing receptors, the activation of which transcriptionally regulates the expression of enzymes and transporters involved in the metabolism and disposition of xenobiotics. Emerging evidence suggests that "xenobiotic receptors" also have diverse endobiotic functions, including their effects on lipid metabolism and energy metabolism. Dyslipidemia is a major risk factor for cardiovascular disease, diabetes, obesity, metabolic syndrome, stroke, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Understanding the molecular mechanism by which transcriptional factors, including the xenobiotic receptors, regulate lipid homeostasis will help to develop preventive and therapeutic approaches. This review describes recent advances in our understanding the atypical roles of three xenobiotic receptors: aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), in metabolic disorders, with a particular focus on their effects on lipid and glucose metabolism. Collectively, the literatures suggest the potential values of AhR, PXR and CAR as therapeutic targets for the treatment of NAFLD, NASH, obesity and diabetes, and cardiovascular diseases.

PMID:36785576 | PMC:PMC9912049 | DOI:10.1515/mr-2022-0032

Arch Toxicol. 2023 Feb 12. doi: 10.1007/s00204-023-03459-7. Online ahead of print.

ABSTRACT

There is a widely recognized need to reduce human activity's impact on the environment. Many industries of the leather and textile sector (LTI), being aware of producing a significant amount of residues (Keßler et al. 2021; Liu et al. 2021), are adopting measures to reduce the impact of their processes on the environment, starting with a more comprehensive characterization of the chemical risk associated with the substances commonly used in LTI. The present work contributes to these efforts by compiling and toxicologically annotating the substances used in LTI, supporting a continuous learning strategy for characterizing their chemical safety. This strategy combines data collection from public sources, experimental methods and in silico predictions for characterizing four different endpoints: CMR, ED, PBT, and vPvB. We present the results of a prospective validation exercise in which we confirm that in silico methods can produce reasonably good hazard estimations and fill knowledge gaps in the LTI chemical space. The proposed protocol can speed the process and optimize the use of resources including the lives of experimental animals, contributing to identifying potentially harmful substances and their possible replacement by safer alternatives, thus reducing the environmental footprint and impact on human health.

PMID:36781432 | DOI:10.1007/s00204-023-03459-7

Psychiatry Res. 2023 Feb 8;321:115102. doi: 10.1016/j.psychres.2023.115102. Online ahead of print.

ABSTRACT

Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given the potential implications of these outcomes and recent proliferation of PGx studies, we conducted a systematic review to evaluate the effectiveness of PGx testing on clinical outcomes in patients with MDD as compared to treatment as usual (TAU). MEDLINE, Embase, PsycInfo, and CENTRAL were searched for English-language articles from 2000 to 2021 for randomized controlled trials (RCTs) comparing PGx-guided treatment vs. TAU in patients with MDD. Meta-analyses were conducted in R. Ten RCTs were included: eight reported remission and seven reported response. The best available evidence suggests that PGx-guided care for moderate-to-severe adult depression is more likely to result in remission and response than TAU (both risk ratios significant). However, there are limitations in the evidence base, including high risk of bias and inconsistency between trials. Despite the consequent very low certainty in the magnitude of effect, there is confidence in the direction. Though modest, the beneficial effects of PGx for adults with moderate-severe MDD could - as a result of the scope and scale of the condition and its impacts - have important ramifications for patients and the health system.

PMID:36780865 | DOI:10.1016/j.psychres.2023.115102

Mol Pharm. 2023 Feb 13. doi: 10.1021/acs.molpharmaceut.2c00715. Online ahead of print.

ABSTRACT

Variants in the SLCO1B1 (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare SLCO1B1 single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime. SLCO1B1 SNVs were annotated with PHRED-scaled combined annotation-dependent (CADD) scores and the Ensembl variant effect predictor. In vitro functionality studies were conducted for the SNVs with a PHRED-scaled CADD score of >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2',7'-dichlorofluorescein (DCF) in OATP1B1-expressing HEK293 cells was measured. According to the findings, additional tests with rosuvastatin and estrone sulfate were conducted. The amount of OATP1B1 in crude membrane fractions was quantified using a liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomics analysis. Six rare missense variants of SLCO1B1 were identified in the study population, located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, SLCO1B1 c.629G>T (p.210G>V) resulted in the loss of in vitro function, abolishing the uptake of DCF, estrone sulfate, and rosuvastatin and reducing the membrane protein expression to 31% of reference OATP1B1. Of the six rare missense variants, SLCO1B1 c.629G>T (p.210G>V) causes a loss of function of OATP1B1 transport in vitro and severely decreases membrane protein abundance. Carriers of SLCO1B1 c.629G>T might be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and might have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.

PMID:36779498 | DOI:10.1021/acs.molpharmaceut.2c00715

Pharmacogenomics. 2023 Feb 13. doi: 10.2217/pgs-2022-0121. Online ahead of print.

ABSTRACT

Aim: To investigate the influence of DDX11-AS1 on paclitaxel (PTX) resistance in lung adenocarcinoma (LUAD). Methods: LncRNA expression and functional enrichment analyses were processed via bioinformatics methods. DDX11-AS1 expression was detected via quantitative real-time PCR. Cell counting kit-8, colony formation, flow cytometry and comet assays were manipulated to measure cell proliferation, apoptosis, cell cycle and DNA damage repair, respectively. Western blot was used to assess DNA damage-related protein expression. Results: DDX11-AS1 was in a high expression status in LUAD, and could promote LUAD cell proliferation and PTX resistance, while suppressing cell apoptosis. DNA damage repairing ability was also modulated by the change of DDX11-AS1 expression. Conclusion: LncRNA DDX11-AS1 promotes DNA damage repair to enhance PTX resistance in LUAD.

PMID:36779347 | DOI:10.2217/pgs-2022-0121

Front Pharmacol. 2023 Jan 26;14:1008330. doi: 10.3389/fphar.2023.1008330. eCollection 2023.

ABSTRACT

Introduction: Next-generation sequencing (NGS) technologies have been widely used in clinical genomic testing for drug response phenotypes. However, the inherent limitations of short reads make accurate inference of diplotypes still challenging, which may reduce the effectiveness of genotype-guided drug therapy. Methods: An automated Pharmacogenomics Annotation tool (PAnno) was implemented, which reports prescribing recommendations and phenotypes by parsing the germline variant call format (VCF) file from NGS and the population to which the individual belongs. Results: A ranking model dedicated to inferring diplotypes, developed based on the allele (haplotype) definition and population allele frequency, was introduced in PAnno. The predictive performance was validated in comparison with four similar tools using the consensus diplotype data of the Genetic Testing Reference Materials Coordination Program (GeT-RM) as ground truth. An annotation method was proposed to summarize prescribing recommendations and classify drugs into avoid use, use with caution, and routine use, following the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC), etc. It further predicts phenotypes of specific drugs in terms of toxicity, dosage, efficacy, and metabolism by integrating the high-confidence clinical annotations in the Pharmacogenomics Knowledgebase (PharmGKB). PAnno is available at https://github.com/PreMedKB/PAnno. Discussion: PAnno provides an end-to-end clinical pharmacogenomics decision support solution by resolving, annotating, and reporting germline variants.

PMID:36778023 | PMC:PMC9909284 | DOI:10.3389/fphar.2023.1008330

Stat Methods Med Res. 2023 Feb 12:9622802231154327. doi: 10.1177/09622802231154327. Online ahead of print.

ABSTRACT

Central to personalized medicine and tailored therapies is discovering the subpopulations that account for treatment effect heterogeneity and are likely to benefit more from given interventions. In this article, we introduce a change plane model averaging method to identify subgroups characterized by linear combinations of predictive variables and multiple cut-offs. We first fit a sequence of statistical models, each incorporating the thresholding effect of one particular covariate. The estimation of submodels is accomplished through an iterative integration of a change point detection method and numerical optimization algorithms. A frequentist model averaging approach is then employed to linearly combine the submodels with optimal weights. Our approach can deal with high-dimensional settings involving enormous potential grouping variables by adopting the sparsity-inducing penalties. Simulation studies are conducted to investigate the prediction and subgrouping performance of the proposed method, with a comparison to various competing subgroup detection methods. Our method is applied to a dataset from a warfarin pharmacogenetics study, producing some new findings.

PMID:36775991 | DOI:10.1177/09622802231154327

J Am Pharm Assoc (2003). 2023 Jan 7:S1544-3191(23)00001-8. doi: 10.1016/j.japh.2023.01.001. Online ahead of print.

ABSTRACT

OBJECTIVES: The primary objective was to identify the proportion of patients who successfully completed PGx testing. Secondary objectives included determining the proportion of patients with actionable PGx results, determining the proportion of patients with a baseline medication intervention within 6 months of successfully completing PGx testing, and identifying barriers for not completing testing.

DESIGN: This was a single center, non-interventional, retrospective cohort study, approved by the institutional review board.

SETTING AND PARTICIPANTS: Patients included were 65 years of age or older and referred for PGx testing from geriatric outpatient clinics between May 1, 2019 and July 31, 2020.

OUTCOME MEASURES: This study aimed to assess the implementation of pharmacist-led pharmacogenomics (PGx) in the care of community-dwelling older adults in an outpatient clinic. Little is known about the acceptance and impact of this type of service within this population.

RESULTS: Of the 67 patients included, majority were female (78%), white (76%), and an average age of 78 years ± 5.98 SD. Majority were insured by Original Medicare or Medicaid (61%), had a history of cognitive impairment (84%), had a referring diagnosis of anxiety (40%) or depression (67%), and were prescribed a selective serotonin reuptake inhibitor (69%) at baseline. Majority successfully completed PGx testing (72%), with 72% having actionable PGx findings and 83% having a pharmacological intervention made thereafter. Nineteen patients did not complete testing (28%), with the primary barrier being not having an appointment scheduled (63%).

CONCLUSION: This study demonstrated majority of older adults were accepting of PGx testing and majority of findings were relevant to clinical care of anxiety, depression, or cognitive impairment.

PMID:36774236 | DOI:10.1016/j.japh.2023.01.001

Maturitas. 2023 Feb 6;170:51-57. doi: 10.1016/j.maturitas.2023.01.013. Online ahead of print.

ABSTRACT

Undeniably, biological age can significantly differ between individuals of similar chronological age. Longitudinal, deep multi-omic profiling has recently enabled the identification of individuals with distinct aging phenotypes, termed 'ageotypes'. This effort has provided a plethora of data and new insights into the diverse molecular mechanisms presumed to drive aging. Translational opportunities stemming from this knowledge continue to evolve, providing an opportunity for the provision of nutritional interventions aiming to decelerate the aging process. In this framework, the contemporary ageotypes classification was revisited via in silico analyses, with the brain and nervous system being identified as the primary targets of age-related biomolecules, acting through inflammatory and metabolic pathways. Nutritional and lifestyle factors affecting these pathways in the brain and central nervous system that could help guide personalized recommendations for the attainment of healthy aging are discussed.

PMID:36773500 | DOI:10.1016/j.maturitas.2023.01.013

J Psychopharmacol. 2023 Feb 11:2698811231152748. doi: 10.1177/02698811231152748. Online ahead of print.

ABSTRACT

BACKGROUND: Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed.

AIMS: To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if CYP2C19 and CYP2D6 genetic variation plays a role.

METHODS: Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. CYP2C19 and CYP2D6 metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates.

RESULTS: Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, p < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, CYP2C19 intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, p = 0.007) and lower triglycerides (-0.17 mmol/L, 95% CI: -0.29 to -0.05, p = 0.007), compared to normal metabolisers.

CONCLUSIONS: Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the CYP2C19 intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline.

PMID:36772859 | DOI:10.1177/02698811231152748

J Clin Med. 2023 Jan 19;12(3):801. doi: 10.3390/jcm12030801.

ABSTRACT

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently associated with a chronic inflammatory state and cardiovascular/metabolic complications. The aim of this study was to evaluate the influence of certain comorbidities on a panel of 45 chemokines and cytokines in OSA patients with special regard to their possible association with cardiovascular diseases.

MATERIAL AND METHODS: This cross-sectional study was performed on 61 newly diagnosed OSA patients. For the measurement of the plasma concentration of chemokines and cytokines, the magnetic bead-based multiplex assay for the Luminex® platform was used.

RESULTS: In the patients with concomitant COPD, there were increased levels of pro-inflammatory cytokines (CCL11, CD-40 ligand) and decreased anti-inflammatory cytokine (IL-10), while in diabetes, there were increased levels of pro-inflammatory cytokines (IL-6, TRIAL). Obesity was associated with increased levels of both pro-inflammatory (IL-13) and anti-inflammatory (IL-1RA) cytokines. Hypertension was associated with increased levels of both pro-inflammatory (CCL3) and anti-inflammatory (IL-10) cytokines. Increased daytime pCO2, low mean nocturnal SaO2, and the oxygen desaturation index were associated with increased levels of pro-inflammatory cytokines (CXCL1, PDGF-AB, TNF-α, and IL-15).

CONCLUSIONS: In OSA patients with concomitant diabetes and COPD, elevated levels of certain pro-inflammatory and decreased levels of certain anti-inflammatory cytokines may favor the persistence of a chronic inflammatory state with further consequences. Nocturnal hypoxemia, frequent episodes of desaturation, and increased daytime pCO2 are factors contributing to the chronic inflammatory state in OSA patients.

PMID:36769452 | DOI:10.3390/jcm12030801