Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity.
paper
Cited
Public
- Authors
- Cservenka, Anita; Yardley, Megan M; Ray, Lara A
- Year
- 2017
- Journal
- The American journal on addictions
- PMID
- 28134463
- DOI
- 10.1111/ajad.12463
- PMCID
- PMC5484746
BACKGROUND AND OBJECTIVES: Pharmacogenetic studies of alcohol use disorder (AUD) have suggested that the efficacy of treatments for AUD is, in part, influenced by the genetic background of an individual. Since the frequency of alleles associated with pharmacotherapy for AUD varies by ancestral background, the effectiveness of medications used to treat AUD may vary among different populations. The purpose of this review is to summarize the existing pharmacogenetic studies of treatments for AUD in individuals of European, East Asian, African, and American Indian/Alaska Native ancestry. METHODS: Electronic databases were searched for pharmacogenetic studies of AUD treatment that included individuals of diverse ancestral backgrounds. RESULTS: Pharmacogenetic studies of AUD reviewed here have primarily investigated genetic variation thought to play a role in the response to naltrexone, ondansetron, and topiramate. There is support that the A118G polymorphism should be further investigated in individuals of East Asian ancestry. DISCUSSION AND CONCLUSIONS: Given the lack of pharmacogenetic research on response to AUD medication in ethnic minority populations and the mixed results, there is a critical need for future studies among individuals of different ancestries. More efforts should be devoted to standardizing procedures such that results can be more readily integrated into a body of literature that can directly inform clinical practice. SCIENTIFIC SIGNIFICANCE: This review highlights the importance for future research to aim for inclusiveness in pharmacogenetic studies of AUD and increase diversity of clinical trials in order to provide the best treatment outcomes for individuals across different racial and ethnic groups. (Am J Addict 2017;26:516-525).
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| # | Section | Preview |
|---|---|---|
| 0 | 1. Introduction | There have been an abundance of both animal and human studies highlighting the importance of genetic… |
| 1 | 1. Introduction | As AUD has a large genetic component, specific risk-conferring genes may be captured through… |
| 2 | 1. Introduction | Among individuals of non-European ancestries, certain genetic polymorphisms have been associated… |
| 3 | 1. Introduction | against alcoholism.11 Furthermore, in Southwest Indians, ADH1 B*3 has shown protective effects… |
| 4 | 1. Introduction | The present review discusses personalized treatment of AUD and considers genetic variation as a… |
| 5 | 2. Existing Health Disparities Among Ethnic Minority Groups | Pharmacotherapies for AUD in ethnic minority populations represent an important line of research in… |
| 6 | 2. Existing Health Disparities Among Ethnic Minority Groups | Americans. Interestingly, after adjusting for demographics and drinking-related variables, the… |
| 7 | 2. Existing Health Disparities Among Ethnic Minority Groups | Not only does it appear that racial-ethnic minorities have lower odds of receiving treatment, but… |
| 8 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries | As noted above, the majority of prior pharmacogenetic studies examining the efficacy of FDA-approved… |
| 9 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | Variations in the μ-opioid receptor (OPRM1) gene and response to NTX are among the most commonly… |
| 10 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | Many studies have examined the A118G SNP and response to NTX in individuals with AUD who are of… |
| 11 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | and NTX compared with medical management and placebo; there was no difference observed between… |
| 12 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | These results, however, are inconsistent with additional reports that found no association between… |
| 13 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | European Americans (73.6%), African Americans accounted for the other 24.4%, which may have also… |
| 14 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | than predicted, namely that NTX would reduce heavy drinking in this group.30 In addition to NTX,… |
| 15 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | In addition to the Asn40Asp polymorphism, research has been conducted on other SNPs that influence… |
| 16 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | per drinking day were lower and percent days abstinent were higher compared to LS/SS participants.… |
| 17 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | Of importance, additional studies have been conducted in attempts to identify novel SNPs that… |
| 18 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry | Specifically, this SNP in GRIK1, appears to moderate the effect of topiramate treatment on drinking… |
| 19 | 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.2 Individuals of East Asian Ancestry | Pharmacogenetic studies of treatment response for AUD in individuals of East Asian ancestry have… |
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| Name | Type |
|---|---|
| 5-HTTLPR | variant |
| A118G SNP | variant |
| acamprosate | drug |
| ADH1B | gene |
| ADH1C | gene |
| Adrenocorticotropin releasing hormone levels local | phenotype |
| African American | cohort |
| AI/AN ancestry local | cohort |
| AI/AN individuals local | cohort |
| alcohol | phenotype |
| alcohol demand | phenotype |
| alcohol dependence | phenotype |
| Alcohol dependence individuals of African ancestry local | cohort |
| Alcohol intervention local | drug |
| alcoholism | phenotype |
| alcohol-related outcomes | phenotype |
| alcohol-related problems | phenotype |
| alcohol sensitivity | phenotype |
| Alcohol treatment services local | drug |
| Alcohol Use Disorder | phenotype |
| ALDH1A1 | gene |
| ALDH2 | gene |
| American Indian/Alaska Native (AI/AN) population local | cohort |
| American Indian/Alaska Native ancestry local | cohort |
| American Indian/Alaskan Native local | cohort |
| American Indians | cohort |
| ancestry | phenotype |
| ancestry-informative markers local | drug |
| anxiety | phenotype |
| Arias et al. study local | cohort |
| Asian | cohort |
| Asian ancestry cohort local | cohort |
| Asian ancestry individuals local | cohort |
| Asn40 local | variant |
| Asp40 local | variant |
| Asp40 allele local | variant |
| AUD | phenotype |
| AUD-associated genes local | gene |
| AUD medication local | drug |
| AUD treatments local | drug |
| binge drinking | phenotype |
| Combine Study | cohort |
| cortisol | drug |
| cortisol response | phenotype |
| craving | phenotype |
| CYP2E1 | gene |
| CYP2E1 c2/C local | variant |
| Daily maximum drinks local | phenotype |
| DAT1 VNTR | variant |
| days abstinent local | phenotype |
| Days abstinent local | phenotype |
| disulfiram | drug |
| drinking-related consequences local | phenotype |
| Drinking-related consequences local | phenotype |
| drinks per week | phenotype |
| East Asian | cohort |
| East Asian Americans and Pacific Islanders local | cohort |
| East Asian ancestry cohort local | cohort |
| East Asian ancestry individuals local | cohort |
| Ethnic minority populations local | cohort |
| European ancestry | cohort |
| European population | cohort |
| Finnish AD cohort local | cohort |
| fluoxetine | drug |
| Flushing response | phenotype |
| GABRA2 | gene |
| Gabrg1 | gene |
| GATA4 | gene |
| genetic markers local | gene |
| Gene variants local | variant |
| GRIK1 | gene |
| GRIK1 A allele local | variant |
| GRIK1 C allele local | variant |
| GRIK1 C/C genotype local | variant |
| GRIK1 SNP local | variant |
| G risk allele local | variant |
| HapMap | cohort |
| healthy controls | cohort |
| heavy drinking | phenotype |
| Heavy drinking individuals of East Asian ancestry local | cohort |
| Hedonic and stimulating effects of alcohol local | phenotype |
| Hedonic and stimulating subjective effects local | phenotype |
| Hispanic | phenotype |
| Hispanic/Latino ancestry local | cohort |
| Htr3a | gene |
| Htr3b | gene |
| immigrant Hispanics local | cohort |
| Individuals of different ancestries local | cohort |
| Individuals of diverse ancestries local | cohort |
| Intensity of demand for alcohol local | phenotype |
| Korean Alcohol Dependence cohort local | cohort |
| Koreans | cohort |
| medical disability local | phenotype |
| Mexican American men local | cohort |
| military participants local | cohort |
| mood disorders | phenotype |
| nalmefene | drug |
| naloxone | drug |
| naltrexone | drug |
| non-European ancestry | cohort |
| nonmilitary participants local | cohort |
| NTX | drug |
| NTX response local | phenotype |
| NTX treatment response local | phenotype |
| number of days abstinent local | phenotype |
| ondansetron | drug |
| ondansetron treatment response local | phenotype |
| OPRM1 | cohort |
| OPRM1 A118G | cohort |
| OPRM1 Asn40 local | variant |
| OPRM1 Asn40Asp polymorphism local | variant |
| OPRM1 Asn40Asp (rs1799971) local | variant |
| OPRM1 Asp40 local | variant |
| OPRM1 Asp40 allele local | variant |
| OPRM1 rs1799971 (Asn40) local | variant |
| OPRM1 rs1799971 (Asp40) local | variant |
| orbitofrontal cortex | anatomy |
| outcome | phenotype |
| Peak breath alcohol concentrations (BrACs) local | phenotype |
| percent days abstinent local | phenotype |
| poor NTX treatment response local | phenotype |
| proportion of abstinent days local | phenotype |
| psychiatric disability local | phenotype |
| psychosis | phenotype |
| race/ethnicity | phenotype |
| Randomized controlled trial local | cohort |
| relapse | phenotype |
| Requests for alcohol during self-administration local | phenotype |
| Response to acamprosate local | phenotype |
| Reward-related craving response local | phenotype |
| rs1042173 local | variant |
| rs1150226 local | variant |
| rs1176713 local | variant |
| rs13273672 | variant |
| rs17614942 local | variant |
| rs1799971 | variant |
| rs2832407 local | variant |
| sertraline | drug |
| sex | phenotype |
| SLC6A3 | gene |
| SLC6A4 | gene |
| Social drinkers of African ancestry local | cohort |
| Southwest California Indians | cohort |
| subsequent drinking after one drink local | phenotype |
| substance use | phenotype |
| time to heavy drinking local | phenotype |
| time until first heavy drinking day local | phenotype |
| topiramate | drug |
| topiramate-induced side effects local | phenotype |
| topiramate serum concentration local | phenotype |
| treatment response | phenotype |
| US born Hispanics local | cohort |
| ventral striatum | anatomy |
| Veterans Affairs Cooperative Study local | cohort |
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. | Mulholland PJ et al. | — | 2023 | → |
| Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. | Juanes RC et al. | — | 2023 | — |
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| Naltrexone and alcohol effects on craving for cigarettes in heavy drinking smokers. | Green R et al. | — | 2019 | → |
| Neuroimaging findings from an experimental pharmacology trial of naltrexone in heavy drinkers of East Asian descent. | Lim AC et al. | — | 2019 | → |
| Pharmacogenetics of alcohol use disorder treatments: an update. | Hartwell EE et al. | — | 2019 | → |
| The paucity of genetic studies of alcohol phenotypes in diverse populations: what are the consequences and opportunities? | Chartier KG | — | 2019 | → |
| Advancing Pharmacotherapy Development from Preclinical Animal Studies. | Egli M | — | 2018 | → |
| Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial. | Ray LA et al. | — | 2018 | → |
| Systemic blockade of LPA<sub>1/3</sub> lysophosphatidic acid receptors by ki16425 modulates the effects of ethanol on the brain and behavior. | Sánchez-Marín L et al. | — | 2018 | → |
| Treatment for Alcohol Use Disorder: Progress in Predicting Treatment Outcome and Validating Nonabstinent End Points. | Creswell KG et al. | — | 2018 | → |
| Commentary: Perspectives on alcohol-related gene and environment interplay in diverse populations. | Scott MS | — | 2017 | → |
| Conclusion: Special issue on genetic and alcohol use disorder research with diverse racial/ethnic groups: Key findings and potential next steps. | Chartier KG et al. | — | 2017 | → |
| Introduction: Special issue on genetic research of alcohol use disorder in diverse racial/ethnic populations. | Chartier KG et al. | — | 2017 | → |