Table 1.
Pharmacogenetic Studies in the Treatment of Alcohol Use Disorder among Diverse Ancestries
| Primary Ancestry | Study | Gene | Polymorphism | Alleles | Allele Frequencies Across Populations | Medication | Sample Size (N) | Gene-by-Medication Findings |
|---|---|---|---|---|---|---|---|---|
| European | Oslin et al., 2003 | OPRM1 | rs1799971 | A/G | CEU (0.85/0.15), JPT (0.51/0.49), ASW (0.95/0.05) | NTX | 141 | ↑ G allele carriers |
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| Gelernter et al., 2007b | OPRM1 | rs1799971 | NTX | 215 | ↔ | |||
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| Anton et al., 2008 | OPRM1 | rs1799971 | NTX | 604 | ↑ G allele carriers | |||
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| Ooteman et al., 2009b | OPRM1 | rs1799971 | NTX | 108 | ↔ | |||
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| Kranzler et al., 2013 | OPRM1 | rs1799971 | NTX | 158 | ↑ G allele carriers | |||
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| Arias et al., 2014b | OPRM1 | rs1799971 | NTX | 107 | ↔ | |||
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| Oslin et al., 2015 | OPRM1 | rs1799971 | NTX | 221 | ↔ | |||
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| Arias et al., 2008b | OPRM1 | rs1799971 | Nalmefene | 272 | ↔ | |||
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| Johnson et al., 2011 | SLC6A4 | 5-HTTLPRd + rs1042173 | A/C | CEU (0.58/0.42), JPT (0.16/0.84), ASW (0.77/0.23) | Ondansetron | 283 |
↑ LL homozygotes ↑ LL/TT homozygotes |
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| Johnson et al., 2013 | SLC6A4, HTR3A, HTR3B | 5-HTTLPR + rs1042173 HTR3A- rs1150226 HTR3A-rs1176713 HTR3B-rs17614942 |
A/G A/G A/C |
CEU (0.05/0.95), JPT (0/1), ASW (0.31/0.69) CEU (0.76/0.24), JPT (0.77/0.23), ASW (0.69/0.31) CEU (0.05/0/0.95), JPT (0/1), ASW (0.11/0.89) |
Ondansetron | 283 | ↑ HTR3A-rs1150226-AG, HTR3A-rs1176713-GG, and/or HTR3B-rs17614942-AC + SLC6A4-LL/TT homozygotes | |
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| Ray et al., 2009 | GRIK1 | rs2832407 | A/C | CEU (0.39/0.61), JPT (0.69/0.31), ASW (0.79/0.21) | Topiramate | 51 | ↑ side effects in A allele carriers | |
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| Kranzler et al., 2014 | GRIK1 | rs2832407 | Topiramate | 138 (122 European) | ↑ C allele homozygotes | |||
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| Asian/East Asian | Kim et al., 2009 | OPRM1 | rs1799971 | NTX | 32 | ↑ G allele carriers | ||
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| Ray et al., 2012 | OPRM1 | rs1799971 | NTX | 35 | ↓craving in G allele carriers | |||
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| Bujarski et al., 2012 | OPRM1 | rs1799971 | NTX | 35 | ↓intensity of alcohol demand in AA homozygotes | |||
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| Africana | Volpicelli et al., 1992 | None | None | NTX | 70 (55 African ancestry) | ↓craving, drinking, relapse | ||
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| Ray & Oslin, 2009 | None | None | NTX | 100 | ↔ | |||
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| Plebani et al., 2011 | None | None | NTX | 43 | ↔on subjective measures of alcohol response | |||
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| AI/AN | O’Malley et al., 2008 | OPRM1 | rs1799971e | NTX, Sertraline | 101 (68 AI/AN) | ↔ | ||
While no gene-by-medication interactions have been investigated in individuals who are primary of African ancestry, studies have investigated response to treatment. Thus, for this population treatment outcomes are listed in the gene-by-medication findings column.
Other genes examined, not discussed here.
Populations selected from the 1000 Genomes Project (Auton, et al., 2015) as examples of different ancestries for reference, and are not meant to be inclusive of all ancestries; CEU = Utah residents with North and Western European ancestry; JPT = Japanese in Tokyo, Japan; ASW = Americans of African ancestry in SW USA.
Extensive information on triallelic frequency for 5-HTTLPR across populations can be found in Haberstick, et al. (2015).
Minor allele frequency for G allele in American Indian sample = 0.13 (Ehlers, Lind, & Wilhelmsen, 2008).
= greater effect or better response to treatment in group indicated; ↔ = no gene-by-medication interaction or medication effect; ↓ = reductions in outcomes indicated; AI/AN = American Indian/Alaska Native, NTX = naltrexone