Opioid Dependence, Susceptibility To, 1

Inheritance

Opioid dependence (OD) is associated with serious medical, legal, social, and psychiatric problems. Risk of OD, like the risk of many other forms of substance dependence, is influenced by genetic factors, as demonstrated by adoption studies (in the general case of substance dependence) and by twin studies. Tsuang et al. (1996) studied more than 3,000 male twin pairs. For most drugs studied (marijuana, stimulants, sedatives, heroin, and other opioids), there was evidence of both shared and specific (unique) risk factors; unique risk factors were most important for heroin abuse.

Mapping

Xu et al. (2004) found association of DRD2 haplotypes (126450), on chromosome 11q23, with vulnerability to heroin dependence in Chinese subjects.

To study the genetic risk of opioid dependence, Gelernter et al. (2006) recruited a sample of 393 small nuclear families, each with at least 1 individual with opioid dependence. As planned a priori to reduce heterogeneity, they used cluster analytic methods to identify opioid dependence-related symptom clusters, which were shown to be heritable. They then completed a genomewide linkage scan for the opioid dependence diagnosis and for the 2 cluster-defined phenotypes represented by more than 250 families: the heavy opioid use cluster and the nonopioid use cluster. The statistically strongest results were seen with the cluster-defined traits. For the heavy opioid use cluster, they observed a lod score of 3.06 on chromosome 17 for European American and African American subjects combined, and, for the nonopioid use cluster, they observed a lod score of 3.46 elsewhere on chromosome 17 for European American subjects only. They also identified a possible linkage (lod score 2.43) of opioid dependence with chromosome 2 markers for the African American subjects.

Clinical Management

Among 98 heroin addicts on methadone maintenance, Levran et al. (2008) found an association between SNPs in the ABCB1 gene (171050) on chromosome 7q21.1 and methadone dose requirements for stability. There was a significant difference in genotype frequency for rs1128503 between those requiring higher dose (greater than 150 mg/day) and those requiring lower doses (less than or equal to 150 mg/day) (p = 0.0325). Individuals bearing the 3-locus genotype pattern TT-TT-TT (rs1045642 (171050.0002), rs2032582, and rs1128503) had a 5-fold increased chance of requiring a higher methadone dose (p = 0.0335) compared to individuals with any other genotype pattern. Individuals heterozygous for these 3 SNPs (CT-GT-CT) had an almost 3-fold increased chance of stabilizing at the lower methadone dose (p = 0.0144) compared to individuals with any other genotype pattern. Levran et al. (2008) suggested that specific ABCB1 variants may have clinical relevance by influencing the methadone dose required to prevent withdrawal symptoms and relapse in this population.

Molecular Genetics

For discussion of a possible association between variation in the OPRM1 gene and opioid dependence, see 600018.

For discussion of a possible association between variation in the OPRD1 gene and opioid dependence, see 165195.