Background:
Cell-cell adhesion is essential in maintaining the structure and function of an organ.
Several adhesion molecules have recently been identified as associated with heroin dependence in both genetic
and peripheral plasma studies.
Methods and Results:
We reviewed literature concerning studies on adhesion molecules in opioid addictions in
rodents and human, including human genetic associations in different ethnic groups, and treatment responses to
methadone maintenance treatment in heroin-dependent patients.
Conclusion:
Some important and novel findings were summarized and discussed. Adhesion molecules in the
peripheral plasma, e.g., cadherin-2 (CDH2), may be biomarkers for both methadone treatment outcome and
nectin 4 may be an indicator for continued opioid use. Neural cell adhesion molecule (NCAM) in the central
nervous system may regulate opioid withdrawal and analgesic responses. Future studies to uncover the mechanisms
underlying the involvement of adhesion molecules in the pathological process of addictions will be an
important research direction in the field.
Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.
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