Pharmacogenomics. 2022 Nov 24. doi: 10.2217/pgs-2022-0077. Online ahead of print.

ABSTRACT

Aim: To explore the roles of lncRNA MALAT1 and SHOC2 in breast cancer, and the potential connections to chemotherapy resistance in breast cancer. Materials & methods: Paclitaxel-resistant breast cancer cells were induced by gradually increasing intermittent doses. Bioinformatic analyses were performed to predict the regulated miRNAs of MALAT1. Results: High expressions of MALAT1 and SHOC2 contribute to paclitaxel resistance in breast cancer cells. MALAT1 sponges miR-497-5p enhance SHOC2 expression in paclitaxel-resistant breast cancer cells and contribute to paclitaxel resistance in breast cancer cells. Conclusion: Patients with high expression of MALAT1 and SHOC2 have a poorer response to paclitaxel. Upregulation of miR-497-5p could improve the treatment response to paclitaxel in patients with breast cancer by inhibiting MALAT1 and SHOC2.

PMID:36420706 | DOI:10.2217/pgs-2022-0077

Fam Pract. 2022 Nov 23:cmac124. doi: 10.1093/fampra/cmac124. Online ahead of print.

ABSTRACT

BACKGROUND: The study of genetic variation as a factor influencing drug safety, efficacy, and effectiveness has brought about significant breakthroughs in understanding the clinical application of gene-drug interactions to better manage drug therapy.

OBJECTIVE: This study was designed to assess the feasibility of collecting buccal samples by general practitioners (GPs) at private practices in Singapore within a usual consultation, incorporating use of a pharmacogenetics-based medical decision support system to guide subsequent drug dosing.

METHODS: We used a prospective cohort study design, with GPs recruiting 189 patients between October 2020 and March 2021. The genotypes of 51 biallelic SNPs were determined using Illumina Infinium Global Screening Array.

RESULTS: Seven GPs from 6 private practices recruited and obtained buccal samples from a total of 189 patients. All patients had at least one actionable variant. The prevalence of patients having 2, 3, or 4 variants was 37.0%, 32.8%, and 12.7%, respectively. Potential alterations to medications were identified using the Clinical Decision Support System. Patients were accepting and the GPs were enthusiastic about the potential of pharmacogenetics to personalize medicine for their patients.

CONCLUSION: This is the first study in Singapore to demonstrate the feasibility of pharmacogenetic testing in primary care. The high prevalence of genetic variants underscores the potential use of pharmacogenetics in this setting.

PMID:36417351 | DOI:10.1093/fampra/cmac124

J Clin Pharmacol. 2022 Nov 23. doi: 10.1002/jcph.2182. Online ahead of print.

NO ABSTRACT

PMID:36416835 | DOI:10.1002/jcph.2182

Expert Rev Respir Med. 2022 Nov 23:1-8. doi: 10.1080/17476348.2022.2149496. Online ahead of print.

ABSTRACT

INTRODUCTION: The study of genetic variants in response to different drugs has predominated in fields of medicine such as oncology and infectious diseases. In chronic respiratory diseases, the available pharmacogenomic information is scarce but not less relevant.

AREAS COVERED: We searched the pharmacogenomic recommendations for respiratory diseases in the Table of Pharmacogenomic Biomarkers in Drug Labeling (U.S. Food and Drug Administration), the Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB. The main pharmacogenomics recommendation in this field is to assess CFTR variants for using ivacaftor and its combination. The drugs' labels for arformoterol, indacaterol, and umeclidinium indicate a lack of influence of genetic variants in the pharmacokinetics of these drugs. Further studies should evaluate the contribution of CYP2D6 and CYP2C19 variants for formoterol. In addition, there are reports of potential pharmacogenetic variants in the treatment with acetylcysteine (TOLLIP rs3750920) and captopril (ACE rs1799752). The genetic variations for warfarin also are presented in PharmGKB and CPIC for patients with pulmonary hypertension.

EXPERT OPINION: The pharmacogenomics recommendations for lung diseases are limited. The clinical implementation of pharmacogenomics in treating respiratory diseases will contribute to the quality of life of patients with chronic respiratory diseases.

PMID:36416606 | DOI:10.1080/17476348.2022.2149496

Per Med. 2022 Nov 23. doi: 10.2217/pme-2022-0041. Online ahead of print.

ABSTRACT

Hyperlipidemia is a significant risk factor for cardiovascular disease morbidity and mortality. The lipid-lowering drugs are considered the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Unfortunately, the lack of efficacy and associated adverse effects, ranging from mild-to-moderate to potentially life-threatening, lead to therapy discontinuation. Numerous reports support the role of gene polymorphisms in drugs' pharmacokinetic parameters and their associated adverse reactions. Therefore, this study aims to understand the pharmacogenomics of lipid-lowering drugs and the impact of genetic variants of key genes on the drugs' efficacy and toxicity. Indeed, genetically guided lipid-lowering therapy enhances overall safety, improves drug adherence and achieves long-term therapy.

PMID:36416179 | DOI:10.2217/pme-2022-0041

Per Med. 2022 Nov 23. doi: 10.2217/pme-2022-0101. Online ahead of print.

ABSTRACT

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training modules that are broadly available for busy clinicians.

PMID:36416152 | DOI:10.2217/pme-2022-0101

Drug Metab Dispos. 2022 Nov 22:DMD-AR-2022-001045. doi: 10.1124/dmd.122.001045. Online ahead of print.

ABSTRACT

The drug 5-fluorouracil (5-FU) is the first-choice chemotherapeutic agent against advanced-stage cancers. However, 10-30% of treated patients experience grade 3-4 toxicity. The deficiency of dihydropyrimidinase (DHPase), which catalyzes the second step of the 5-FU degradation pathway, is correlated with the risk of developing toxicity. Thus, genetic polymorphisms within DPYS, the DHPase-encoding gene, could potentially serve as predictors of severe 5-FU-related toxicity. We identified 12 novel DPYS variants in 3,554 Japanese individuals, but the effects of these mutations on function remain unknown. In the current study, we performed in vitro enzymatic analyses of the 12 newly identified DHPase variants. Dihydrouracil or dihydro-5-FU hydrolytic ring-opening kinetic parameters, Km and Vmax , and intrinsic clearance (CLint = Vmax /Km ) of the wild-type DHPase and eight variants were measured. Five of these variants (R118Q, H295R, T418I, Y448H, and T513A) showed significantly reduced CLint compared with that in the wild-type. The parameters for the remaining four variants (V59F, D81H, T136M, and R490H) could not be determined as dihydrouracil and dihydro-5-FU hydrolytic ring-opening activity was undetectable. We also determined DHPase variant protein stability using cycloheximide and bortezomib. The mechanism underlying the observed changes in the kinetic parameters was clarified using blue-native polyacrylamide gel electrophoresis and three-dimensional structural modeling. The results suggested that the decrease or loss of DHPase enzymatic activity was due to reduced stability and oligomerization of DHPase variant proteins. Our findings support the use of DPYS polymorphisms as novel pharmacogenomic markers for predicting severe 5-FU-related toxicity in the Japanese population. Significance Statement DHPase contributes to the degradation of 5-fluorouracil, and genetic polymorphisms that cause decreased activity of DHPase can cause severe toxicity. In this study, we performed functional analysis of 12 DHPase variants in the Japanese population and identified 9 genetic polymorphisms that cause reduced DHPase function. In addition, we found that the ability to oligomerize and the conformation of the active site are important for the enzymatic activity of DHPase.

PMID:36414408 | DOI:10.1124/dmd.122.001045

Pediatr Emerg Care. 2022 Nov 23. doi: 10.1097/PEC.0000000000002871. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the study was to evaluate the ability of a combinatorial pharmacogenomic test to predict medication blood levels and relative clinical improvements in a selected pediatric population.

METHODS: This study enrolled patients between ages 3 to 18 years who presented to a pediatric emergency department with acute psychiatric, behavioral, or mental health crisis and/or concerns, and had previously been prescribed psychotropic medications. Patients received combinatorial pharmacogenomic testing with medications categorized according to gene-drug interactions (GDIs); medications with a GDI were considered "incongruent," and medications without a GDI were considered "congruent." Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine were evaluated according to level of GDI. Relative clinical improvements in response to the prescribed psychotropic medications were measured using a parent-rated Clinical Global Impression of Improvement (CGI-I) assessment, where lower scores corresponded with greater improvement.

RESULTS: Of the 100 patients enrolled, 73% reported taking ≥1 incongruent medication. There was no significant difference in CGI-I scores between patients prescribed congruent versus incongruent medications (3.37 vs 3.68, P = 0.343). Among patients who presented for depression or suicidal ideation, those prescribed congruent medications had significantly lower CGI-I scores compared with those taking incongruent medications (P = 0.036 for depression, P = 0.018 for suicidal ideation). There was a significant association between medication GDI and blood levels for aripiprazole (n = 15, P = 0.01) and escitalopram (n = 10, P = 0.01).

CONCLUSIONS: Our preliminary findings suggest that combinatorial pharmacogenomic testing can predict medication blood levels and relative outcomes based on medication congruency in children presenting to an emergency department with acute psychiatric/behavioral crises. Additional studies will be needed to confirm these findings.

PMID:36413430 | DOI:10.1097/PEC.0000000000002871

Proteomics. 2022 Nov 22:e2200176. doi: 10.1002/pmic.202200176. Online ahead of print.

ABSTRACT

It is challenging to study regulatory genetic variants as gene expression is affected by both genetic polymorphisms and non-genetic regulators. The mRNA allele-specific expression (ASE) assay has been increasingly used for the study of cis-acting regulatory variants because cis-acting variants affect gene expression in an allele-specific manner. However, poor correlations between mRNA and protein expressions were observed for many genes, highlighting the importance of studying gene expression regulation at the protein level. In the present study, we conducted a proof-of-concept study to utilize a recently developed allele-specific protein expression (ASPE) assay to identify the cis-acting regulatory variants of CES1 using a large set of human liver samples. The CES1 gene encodes for carboxylesterase 1 (CES1), the most abundant hepatic hydrolase in humans. Two cis-acting regulatory variants were found to be significantly associated with CES1 ASPE, CES1 protein expression, and its catalytic activity on enalapril hydrolysis in human livers. Compared to conventional gene expression-based approaches, ASPE demonstrated an improved statistical power to detect regulatory variants with small effect sizes since allelic protein expression ratios are less prone to the influence of non-genetic regulators (e.g., diseases and inducers). This study suggests that the ASPE approach is a powerful tool for identifying cis-regulatory variants. This article is protected by copyright. All rights reserved.

PMID:36413357 | DOI:10.1002/pmic.202200176

Pharmacy (Basel). 2022 Oct 26;10(6):139. doi: 10.3390/pharmacy10060139.

ABSTRACT

BACKGROUND: Despite evidence of clinical utility and the availability of prescription guidelines, pharmacogenomics (PGx) is not broadly used in institutional settings in Canada. To inform future implementation, this study aimed to identify healthcare provider knowledge, experience, and perceptions of PGx in Alberta, Canada.

METHODS: An online 44-item survey was distributed to pharmacists, nurse practitioners, and physicians employed or contracted with Alberta Health Services from January to May 2022. Questions included: demographics, professional history, PGx education and exposure, knowledge, and ability to use PGx, and attitudes towards, feasibility, clinical utility, education, and implementation.

RESULTS: Ninety-one pharmacists, 37 nurse practitioners, and 6 physicians completed the survey. Fifty-nine percent had 10 or more years of experience, and 71% practiced in urban settings. Only one-third had training in PGx, and one-quarter had used PGx. Most respondents (63%) had no knowledge of PGx resources, including the Pharmacogenomics Knowledge Base (75%), or the Clinical Pharmacogenetics Implementation Consortium guidelines (85%). While participants agreed that they understood genetic (75%) and PGx (63%) concepts, most disagreed with their ability regarding practical applications of PGx such as translating genotype to phenotype (74%) or counselling patients on results (66%). Participants agreed on the clinical utility of PGx in preventing adverse drug reactions (80%) and enhancing medication efficacy (77%), and identified oncology (62%), cardiovascular/stroke (60%), and psychiatry (56%) as therapeutic areas to consider implementation. At present, healthcare provider knowledge (87%), cost (81%), and limited guidelines/evidence (70%) are seen as the greatest barriers to implementation.

CONCLUSION: Alberta healthcare providers have limited training, experience, or knowledge in PGx. However, most appear to have a positive outlook regarding clinical utility, especially within oncology, cardiology, and psychiatry. More effort is required to socialize the availability and quality of evidence and guidelines for the interpretation of PGx test results, address other knowledge gaps, and improve financial limitations.

PMID:36412815 | DOI:10.3390/pharmacy10060139

J Xenobiot. 2022 Oct 28;12(4):317-328. doi: 10.3390/jox12040022.

ABSTRACT

BACKGROUND: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions.

METHODS: 108 hospitalized patients with major depressive disorder were genotyped for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, NAT2, DPYD; VKORC1 and TMTP.

RESULTS: We found 583 (mean 5.4, median 5) divergent phenotypes (i.e., divergent from the common phenotypes considered normal, e.g., extensive metabolizer) in the 12 analyzed pharmacokinetic genes. The rate for at least one divergent phenotype was 100% in our cohort for CYP, but also for all 12 important pharmacogenes: patients had at least two divergent phenotypes. Compared to a large Danish cohort, CYP2C9 NM and IM status, CYP2C19 UM, CYP2D6 UM and DYPD (GAS 0, 1, 2) genotypes differed statistical significantly. For CYP2D6 and CYP2C19, 13% of the patients were normal metabolizers for both enzymes in our cohort, but this value was 27.3% in the Danish cohort, which is a highly significant difference (p < 0.0001).

CONCLUSION: Divergent phenotypes in pharmacogenes are not the exception, but the rule. Patients with divergent phenotypes seem more prone for hospitalization, emphasizing the need for pre-emptive testing to avoid inefficacy and adverse drug effects in all patients.

PMID:36412766 | DOI:10.3390/jox12040022

Pharmacogenomics. 2022 Nov 22. doi: 10.2217/pgs-2022-0161. Online ahead of print.

NO ABSTRACT

PMID:36412207 | DOI:10.2217/pgs-2022-0161

J Lipid Res. 2022 Nov 18:100316. doi: 10.1016/j.jlr.2022.100316. Online ahead of print.

ABSTRACT

The large high-density lipoprotein (HDL) particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport (RCT). Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the low-density lipoprotein receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P<0.01), and in turn raised large apo E-containing HDL by 66% (P<0.001) and 59% (P<0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P<0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P<0.001) and apo B-depleted plasma apo E (+24%, P<0.001), leading to the formation of apo E-containing HDL (+47%, P<0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increase large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.

PMID:36410424 | DOI:10.1016/j.jlr.2022.100316

Cancer Immunol Res. 2022 Nov 21:CIR-22-0260. doi: 10.1158/2326-6066.CIR-22-0260. Online ahead of print.

ABSTRACT

The ectonucleotidases CD39 and CD73 catalyze extracellular adenosine triphosphate (ATP) to immunosuppressive adenosine (ADO), and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells. In mouse transplanted KPC tumors, both CD39 and CD73 on myeloid cells, as well as CD73 on tumor cells, promoted polarization of infiltrating myeloid cells towards an M2-like phenotype, which enhanced tumor growth. CD39 on tumor-specific CD8+ T cells and pancreatic stellate cells also suppressed IFN production by T cells. Although therapeutic inhibition of CD39 or CD73 alone significantly delayed tumor growth in vivo, targeting of both ectonucleotidases exhibited markedly superior anti-tumor activity. CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Accordingly, large-scale pharmacogenomic analyses of human PDAC cell lines revealed significant associations between CD73 expression and gemcitabine chemoresistance. Strikingly, increased DNA damage in CD73-deficient tumor cells associated with activation of the cGAS-STING pathway. Moreover, cGAS expression in mouse KPC tumor cells was required for anti-tumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.

PMID:36409930 | DOI:10.1158/2326-6066.CIR-22-0260

Pharmacogenomics. 2022 Nov 21. doi: 10.2217/pgs-2022-0123. Online ahead of print.

ABSTRACT

Aim: To investigate the influence of CYP3A5 and IL-10 polymorphisms on tarcolimus metabolism and renal function for renal transplantation recipients at a stable period. Methods: CYP3A5 and IL-10 polymorphisms, together with other clinical factors, were collected for 149 renal transplantation patients at postoperative stable period. Statistics analysis was performed to explore key factors affecting tarcolimus metabolism. Results: CYP3A5 6986A >G and IL-10 -819C >T significantly impacted tacrolimus metabolism (p < 0.001). CYP3A5 6986A >G G allele and IL-10 -819C >T T allele were associated with poorer tacrolimus metabolic capability. Patients with various tacrolimus metabolism rates presented little difference in renal functions at stable period. Conclusion: Genotyping of CYP3A5 and IL-10 might benefit the precision dosage of tacrolimus for renal transplantation recipients.

PMID:36408735 | DOI:10.2217/pgs-2022-0123

Am J Chin Med. 2022 Nov 21:1-21. doi: 10.1142/S0192415X23500076. Online ahead of print.

ABSTRACT

Gut microbiota are significantly associated with the occurrence and development of inflammatory bowel disease (IBD). Panax notoginseng saponins (PNS) could be used for colitis and to modulate gut microbiota. However, the mechanism behind the effects of PNS on anti-colitis that are pertinent to gut microbiota is largely unknown. This study aimed to evaluate the anti-colitis effects of PNS and explore the involved mechanism as it is related to gut microbiota. Results showed that PNS significantly alleviated dextran sulfate sodium (DSS)-induced colitis. Meanwhile, after PNS treatment, the tight junction proteins were enhanced and proinflammatory cytokines, such as TNF-[Formula: see text], IL-6, IL-1[Formula: see text], and IL-17, were decreased. Furthermore, Bacteroides spp. were significantly increased after modeling, while PNS reduced their abundance and significantly increased the amount of Akkermansia spp. in vivo. Importantly, Akkermansia spp. and Bacteroides spp. were correlated with the IBD disease indicators. Moreover, fecal microbiota transplantation (FMT) experiments confirmed that PNS-reshaped gut microbiota significantly alleviated DSS-induced colitis, while A. muciniphila significantly reduced the levels of the LPS-induced cellular inflammatory factors IL-1[Formula: see text] and TNF-[Formula: see text]. In conclusion, PNS alleviated colitis pertinent to the upregulation of Akkermania spp. and downregulation of Bacteroides spp. in the gut.

PMID:36408726 | DOI:10.1142/S0192415X23500076

Complex Psychiatry. 2021 Dec;7(3-4):80-89. doi: 10.1159/000519707. Epub 2021 Nov 18.

ABSTRACT

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.

PMID:36408127 | PMC:PMC8740189 | DOI:10.1159/000519707

Ment Health Clin. 2022 Nov 3;12(5):270-281. doi: 10.9740/mhc.2022.10.270. eCollection 2022 Oct.

ABSTRACT

There are now 9 available FDA-approved second-generation long-acting injectable antipsychotics including aripiprazole (3), olanzapine (1), paliperidone (3), and risperidone (2). These high-cost medications are commonly used with the goal of improving adherence and patient outcomes. With almost 2 decades of use, key aspects have been well studied, including population pharmacokinetics, CYP interactions and various clinical and economic outcomes. However, there are still unknowns with these medications. Issues including adherence, transition from oral antipsychotics, renal dosing, pharmacogenomics, and managing missed doses will be addressed in the context of 4 patient cases.

PMID:36405505 | PMC:PMC9645288 | DOI:10.9740/mhc.2022.10.270

Animal Model Exp Med. 2022 Nov 20. doi: 10.1002/ame2.12291. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is a polygenic metabolic disease, characterized by high fasting blood glucose (FBG). The ability of cranberry (CRN) fruit to regulate glycemia in T2D patients is well known. Here, a cohort of 13 lines of the genetically diverse Collaborative Cross (CC) mouse model was assessed for the effect of non-dialyzable material (NDM) of cranberry extract in lowering fasting blood glucose.

METHODS: Eight-week-old mice were maintained on either a standard chow diet (control group) or a high-fat diet (HFD) for 12 weeks, followed by injections of intraperitoneal (IP) NDM (50 mg/kg) per mouse, three times a week for the next 6 weeks. Absolute FBG (mg/dl) was measured bi-weekly and percentage changes in FBG (%FBG) between weeks 0 and 12 were calculated.

RESULTS: Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD. However, a non-significant increase in FBG values was observed in male and female mice maintained on HFD during the same period. Following administration of NDM during the following 6 weeks, the results show a variation in significant levels of FBG lowering between lines, male and female mice and under the different diets.

CONCLUSION: The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background (pharmacogenetics), sex of the mouse (pharmacosex), and diet (pharmacodiet). All these results support the need for follow-up research to better understand and implement a personalized medicine approach/utilization of NDM for reducing FBG.

PMID:36404387 | DOI:10.1002/ame2.12291

J Allergy Clin Immunol Pract. 2022 Nov 17:S2213-2198(22)01194-1. doi: 10.1016/j.jaip.2022.10.048. Online ahead of print.

ABSTRACT

BACKGROUND: While food allergies are considered common, relatively little is known about disparities in food allergy by race in the United States.

OBJECTIVE: To evaluate differences in reported food allergy and food-associated anaphylaxis among individuals enrolled in a longitudinal cohort study from metropolitan Detroit, Michigan.

METHODS: Participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) were asked about food allergies, including the inciting food and associated symptoms. Individuals were considered to have food-associated anaphylaxis if symptoms coincided with established clinical criteria. Logistic regression was used to assess whether race difference persisted after adjusting for and stratifying by potential confounders. African genetic ancestry was individually estimated among African American SAPPHIRE participants to assess whether ancestry was associated with food allergy.

RESULTS: Within the SAPPHIRE cohort, African American participants were significantly more likely to report food allergy (26.1% vs. 17%; P=3.47x10-18) and have food-associated anaphylactic symptoms (12.7% vs. 7%; P=4.65x10-14) when compared with European American participants. Allergy to seafood accounted for the largest difference (13.1% vs. 4.6%; P=1.38x10-31). Differences in food allergy by race persisted after adjusting for potential confounders including asthma status. Among African American participants, proportion of African ancestry was not associated with any outcome evaluated.

CONCLUSION: Compared with European Americans, African Americans appear to be at higher risk for developing food allergy and food-associated anaphylaxis, particularly with regard to seafood allergy. The lack of association with genetic ancestry suggests that socio-environmental determinants may play a role in these disparities.

PMID:36403896 | DOI:10.1016/j.jaip.2022.10.048