Frequency of the Dopamine Receptor D3 (rs6280) vs. Opioid Receptor µ1 (rs1799971) Polymorphic Risk Alleles in Patients with Opioid Use Disorder: A Preponderance of Dopaminergic Mechanisms?

Gondré–Lewis, Marjorie C.; Elman, Igor; Alim, Tanya N.; Chapman, Edwin; Settles-Reaves, Beverlyn; Galvao, Carine; Gold, Mark S.; Baron, David; Kazmi, Shan; Gardner, Eliot L.; Gupta, Ashim; Dennen, Catherine A.; Blum, Kenneth

doi:10.3390/biomedicines10040870

Cited by 10 publications

(5 citation statements)

References 104 publications

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“…Treatment approaches that are one-size-fits-all based on regimen developed with White research participants and few to no African Americans must be carefully vetted, as discussed by our group in Abijo et al, Gondré-Lewis et al, and Limgala et al [27,51,52]. Vulnerability to cancers, systemic, and psychiatric disorders can vary by ethnicity, but opioid addiction can as well [53,54].…”

Section: Discussionmentioning

confidence: 99%

The Opioid Epidemic: a Crisis Disproportionately Impacting Black Americans and Urban Communities

Gondré–Lewis

Abijo

Gondré-Lewis

2022

J. Racial and Ethnic Health Disparities

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The heroin epidemic has existed for decades, but a sharp rise in opioid overdose deaths (OODs) jolted the nation in the mid-twenty-teens and continues as a major health crisis to this day. Although the new wave of OODs was initially approached as a rural problem impacting a White/Caucasian demographic, surveillance records suggest severe impacts on African Americans and urban-dwelling individuals, which have been largely underreported. The focus of this report is on specific trends in OOD rates in Black and White residents in states with a significant Black urban population and declared as hotspots for OOD: (Maryland (MD), Illinois (IL), Michigan (MI), and Pennsylvania (PA)), and Washington District of Columbia (DC). We compare OODs by type of opioid, across ethnicities, across city/rural demographics, and to homicide rates using 2013–2020 data acquired from official Chief Medical Examiners’ or Departments of Health (DOH) reports. With 2013 or 2014 as baseline, the OOD rate in major cities (Baltimore, Chicago, Detroit, Philadelphia) were elevated two-fold over all other regions of their respective state. In DC, Wards 7 and 8 OODs were consistently greater than other jurisdictions, until 2020 when the rate of change of OODs increased for the entire city. Ethnicity-wise, Black OOD rates exceeded White rates by four- to six-fold, with fentanyl and heroin having a disproportionate impact on Black opioid deaths. This disparity was aggravated by its intersection with the COVID-19 pandemic in 2020. African Americans and America’s urban dwellers are vulnerable populations in need of social and political resources to address the ongoing opioid epidemic in under-resourced communities. Supplementary Information The online version contains supplementary material available at 10.1007/s40615-022-01384-6.

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Section: Discussionmentioning

confidence: 99%

The Opioid Epidemic: a Crisis Disproportionately Impacting Black Americans and Urban Communities

Gondré–Lewis

Abijo

Gondré-Lewis

2022

J. Racial and Ethnic Health Disparities

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“…The COMT gene showed varied expression among heroin addicts. The DRD1 and DRD3 gene variations were linked to early-onset heroin dependence, indicating susceptibility to addiction (11). Previous research indicated conflicting findings regarding DRD5 and DRD4 (12).…”

Section: Discussionmentioning

confidence: 99%

Predictive Factors for Methadone Maintenance Treatment Compliance: Exploring Resistance and Tolerance in Heroin Addiction

Makvand,

Mirtorabi,

Campbell

et al. 2024

Iran J Psychiatry Behav Sci

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Background: Methadone maintenance treatment (MMT) has been a cornerstone in heroin addiction management. However, its efficacy varies among individuals. The complex interplay of genetic backgrounds and demographic data could influence the response to MMT in heroin addiction. No previous adoption study has aimed to merge these findings into a potential pre-treatment screening tool. Objectives: This study aimed to investigate the combined influence of dopamine and opioid receptors and receptor endocytosis machinery genes, individual genetic backgrounds, and demographic data on the response to MMT in patients with heroin addiction. Methods: We enrolled 80 heroin addicts receiving MMT for 3 months alongside 80 healthy individuals in a comparative study. The approach utilized multinomial, linear, and binary logistic regression analyses to investigate the interplay of genetic factors (DRD1-5, opioid receptors [µ1, δ1, and κ1], DNM1L, RAB22A, and COMT), demographic independent variables, including, family history, heroin duration, age onset, heroin dose, and methadone dose, and clinical markers Subjective Opiate Withdrawal Scale (SOWS) with compliance with MMT protocols. Results: Results revealed that a positive family history and a higher level of heroin dose significantly predicted poor compliance to MMT. Additionally, the patients with lower expression levels of DRD2 and higher expression levels of DNM1L and COMT genes were at higher risk for poor compliance with the treatment. Conclusions: By utilizing a comprehensive dataset of gene expression profiles and demographic and clinical parameters, this study developed a regression model predicting resistance or response to methadone. This innovative approach seeks to bridge the gap between pharmacogenomics and clinical practice and offer a potential pre-treatment screening tool for personalized MMT strategies in opioid addiction management. The obtained findings hold intriguing promise for future research, potentially unlocking deeper insights into the underlying risk factors of addiction.

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“…The development of this genetic assessment was initiated by Blum's laboratory in 2014 published in Molecular Neurobiology [33]. Since that time the same authors have published human trials concerning various applications of GARS in clinical medicine with significantly significant results [11,13,14,16,[65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Moreover, since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS.…”

Section: Limitationsmentioning

confidence: 99%

The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research

Thanos

Hanna²,

Mihalkovic

et al. 2023

JPM

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It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = −0.4983, p < 0.05) and PSQI scores (r = −0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery.

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Frequency of the Dopamine Receptor D3 (rs6280) vs. Opioid Receptor µ1 (rs1799971) Polymorphic Risk Alleles in Patients with Opioid Use Disorder: A Preponderance of Dopaminergic Mechanisms?

Cited by 10 publications

References 104 publications

The Opioid Epidemic: a Crisis Disproportionately Impacting Black Americans and Urban Communities

The Opioid Epidemic: a Crisis Disproportionately Impacting Black Americans and Urban Communities

Predictive Factors for Methadone Maintenance Treatment Compliance: Exploring Resistance and Tolerance in Heroin Addiction

The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research

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