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.
Highlights
Pharmacogenomics study has recently received recognition for its potential application in personalized medicine [1]
We developed a new method by starting genetic variant association analyses, determining the plasma levels of proteins encoded by the candidate genes, examining the protein-phenotype correlations in a Taiwanese methadone maintenance treatment (MMT) population
We identified a significant correlation between the Cadherin 2 (CDH2) protein network and its metabolic enzyme ADAM metallopeptidase domain 10 (ADAM10) and cytokine IL-7 through systemic relation analyses in the present study
Summary
Pharmacogenomics study has recently received recognition for its potential application in personalized medicine [1]. One of the methods in pharmacogenomic analysis is to build pathway network and observe gene-gene interaction status contributing to treatment responses This kind of analysis often misses the opportunity to discover novel plasma proteins that may serve as potential biomarkers toward treatment response. We developed a new method by starting genetic variant association analyses, determining the plasma levels of proteins encoded by the candidate genes, examining the protein-phenotype (treatment responses) correlations in a Taiwanese methadone maintenance treatment (MMT) population. Through this new approach, we were able to identified novel network among the gene encoding proteins involving cardiovascular function, inflammatory factors, and MMT treatment responses. We identified a significant correlation between the CDH2 protein network and its metabolic enzyme ADAM10 and cytokine IL-7 through systemic relation analyses in the present study
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