Table 4.
Genetic variants associated with opioid use disorder treatment response
| Drug | Ethnicity | Measurement | Gene | Variant/ allele |
MAF (minor allele)a |
Finding | Reference |
|---|---|---|---|---|---|---|---|
| Methadone | African-American (n = 36) | Urine drug screens for opioids | OPRD1 | rs678849 | 26% (T) | T allele increased risk for positive tests | [76] |
| Methadone | European-American (n = 283) | Urine drug screens for opioids | OPRM1 | rs10485058 | 15% (G) | G allele increased risk for positive tests | [77] |
| Methadone | Taiwanese (n = 360) | Urine drug screen for morphine | CDH2 | rs8094439 | 21% (A) | A/A associated with increased CDH2 plasma levels | [78] |
| rs17446819 | 21% (C) | C/C associated with increased CDH2 plasma levels | |||||
| Increased plasma level correlated with increased risk of positive test | |||||||
| Methadone | European (n = 169) | Responder = no opioid-positive urines in last 4 tests. | MYOCD | rs1714984 | 23% (A) | Carrying the A allele at rs1714984 and the A/G | [81] |
| Non-responder = 2 or more tests positive in last 4 | GRM6 | rs953741 | 34% (G) | genotype at rs953741 increased risk of being non-responder | |||
| Methadone | European (n = 169) | Responder = no opioid-positive urines in last 4 tests. Non-responder = 2 or more tests positive in last 4 | ALDH5A1 | rs2760118 | 32% (T) | T allele increased risk of being non-responder | [82] |
| Methadone | European (n = 238) | Responder = 1 or fewer positive weekly urine drug screens in last 3 months. Non-responder = regular opioid and/or cocaine use in last 3 months | DRD2 | rs6277 | 46% (C) | C/C genotype increased risk of being non-responder | [84] |
| Methadone | European-Australian (n = 95) | Successful outcome = continued use of methadone with reduced heroin use or planned completion of methadone treatment without heroin use. Poor outcome = dropping out of treatment or using heroin at least weekly | DRD2 | rs1800497 | 19% (T) | T allele associated with increased risk of poor outcome | [87] |
| Methadone | European (n = 238) | Responder = 1 or fewer positive weekly urine drug screens in last 3 months and absence of withdrawal symptoms. Non-responder = regular opioid and/or cocaine use in last 3 months | ARRB2 | rs3786047 | 32% (A) | Minor allele homozygotes for all variants increased risk of being non-responder | [83] |
| rs1045280 | 31% (C) | ||||||
| rs2036657 | 32% (G) | ||||||
| Methadone | European (n = 91) | Responder = no opioid-positive urines in last 4 tests. Non-responder = 2 or more tests positive in last 4 | BDNF | rs7127507 | 30% (C) | CCGCCG haplotype increased risk of being a non-responder | [88] |
| rs1967554 | – | ||||||
| rs11030118 | – | ||||||
| rs988748 | 24% (C) | ||||||
| rs2030324 | 48% (G) | ||||||
| rs11030119 | 28% (A) | ||||||
| Methadone | Taiwanese (n = 366) | Clinical Opioid Withdrawal Scale | UGT2B7 | rs6600879 | 31% (C) | Major allele homozygotes associated with increased withdrawal symptoms | [90] |
| rs6600880 | 31% (T) | ||||||
| rs4554144 | 31% (C) | ||||||
| rs11940316 | 31% (T) | ||||||
| rs7438135 | 31% (G) | ||||||
| rs7662029 | 31% (A) | ||||||
| rs7668258 | 31% (T) | ||||||
| rs7439366 | 31% (T) | ||||||
| rs4292394 | 31% (C) | ||||||
| rs6600893 | 31% (T) | ||||||
| Methadone | Taiwanese (n = 366) | Clinical Opioid Withdrawal Scale | OPRK1 | rs7832417 | 7% (T) | TTCT haplotype increased bone or joint ache symptoms | [89] |
| rs16918853 | 7% (T) | ||||||
| rs702764 | 7% (C) | ||||||
| rs7817710 | 7% (T) | ||||||
| rs10958350 | 11% (A) | Haplotypes associated with gooseflesh, yawning, and restlessness | |||||
| rs7016778 | 11% (T) | ||||||
| rs12675595 | 12% (A) | ||||||
| Methadone | European (n = 85) | Withdrawal symptoms by clinical assessment | KCNJ6 | rs2070995 | 20% (T) | A/A genotype reduced withdrawal symptoms | [66] |
| Methadone | European (n = 205) | Verona Service Satisfaction Scale | CYP2D6 | *1 × 2 | 1% (–)b | Ultrarapid metabolism status decreased satisfaction | [91] |
| *2 × 2 | 2% (–)b | ||||||
| Buprenorphine /naloxone | African-American (n = 41) | Urine drug screens for opioids | OPRD1 | rs678849 | 26% (T) | T allele decreased risk for positive tests | [76] |
| Buprenorphine /naloxone | European-American (female; n = 81) | Urine drug screens for opioids | OPRD1 | rs581111 | 28% (A) | A allele increased risk for positive tests | [93] |
| rs529520 | 45% (A) | A/A genotype increased risk for positive tests | |||||
| Buprenorphine | European (n = 107) | Non-responder = any of the following: drop out in first 12 weeks, ≥33% urine drug screens positive for opioids or cocaine, behavioral problems resulting in | SLC6A3 | 3’ UTR VNTR | – | 11-repeat allele decreased risk of being a non-responder | [96] |
a
Estimates from 1000 Genomes Project
b
Frequency from study population
MAF predicted minor allele frequency in study ethnicity, UTR untranslated region, VNTR variable number tandem repeat