Abstract
We previously reported a high plasma chemokine interferon gamma-inducible protein 10 (IP-10) level and prolonged electrocardiography QT-interval in methadone maintenance treatment (MMT) patients with HIV or HCV infection. The purpose of this study was to evaluate the genetic association of high plasma IP-10 level in the MMT patients. The gene-based and pathway-based association analyses were conducted using a genome-wide association study dataset in 344 MMT patients for identifying genes and pathways associated with plasma IP-10 level. We found that plasma IP-10 level was significantly associated with a pathway in the tight junction (P = 1.01x10-5), where the claudin 8 (CLDN8) gene had the most significant association (P = 6.8x10-5). A functional single nucleotide polymorphism (SNP) rs686364 at exon 1 of CLDN8 showed strong association with plasma IP-10 levels, in the MMT subjects with positive urine test for morphine (dominant model, P = 0.00004). The minor allele type carriers had higher plasma IP-10 levels than the major allele type carriers. Our data support that the tight junction protein claudin 8 exon 1 is a predictor for the plasma levels of IP-10 in MMT patients with urine test positive for morphine.
Highlights
Methadone is a synthetic opioid used for the treatment of heroin dependence [1,2,3]
High plasma or serum inducible protein 10 (IP-10) was found in patients with lymphoproliferative disorder [11], systemic lupus erythematosus [12], HIV infection [16], or Kawasaki disease of acute vasculitis [15]
We identified a pathway with genome-wide significance and pinpointed a candidate gene correlating the plasma levels of IP-10 in maintenance treatment (MMT) patients
Summary
Methadone is a synthetic opioid used for the treatment of heroin dependence [1,2,3]. We previously reported a high prevalence of hepatitis C viral (HCV, 95%) and human immunodeficiency virus (HIV, 23%) infection in a methadone maintenance treatment (MMT) population in Taiwan [4]. These HCV or HIV patients showed an increase in plasma levels of chemokine interferon gamma-inducible protein 10 (IP-10; called chemokine CXC motif ligand 10; CXCL10) [5, 6]. High plasma IP-10 level correlated with the prolonged.
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