Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome

Abstract

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.

Fig 1. A schematic design from a pharmacogenomic study in methadone maintenance therapy.

This design has led to systemic discovery of some hidden pathways among plasma IL-7, ADAM10 and CDH2, and their contributions to the methadone treatment responses.

Fig 2. Correlation matrix heatmap of the study variables.

Spearman correlation coefficients are presented by a blue-white-red color scheme. Dark red indicates a more positive correlation; dark blue indicates a more negative correlation; white indicates no correlation.