Missense mutation at CLDN8 associated with a high plasma interferon gamma-inducible protein 10 level in methadone-maintained patients with urine test positive for morphine

PLoS One. 2017 Nov 16;12(11):e0187639. doi: 10.1371/journal.pone.0187639. eCollection 2017.

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.

MeSH terms

  • Adult
  • Chemokine CXCL10 / blood*
  • Claudins / genetics*
  • Female
  • Humans
  • Male
  • Methadone / administration & dosage*
  • Morphine / administration & dosage
  • Morphine / urine*
  • Mutation, Missense*
  • Opiate Substitution Treatment*
  • Substance Abuse Detection / methods*

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10
  • Claudins
  • Morphine
  • claudin 8
  • Methadone

Grants and funding

This study was provided by the National Research Program for Genomic Medicine [NSC 100-3112-B-400-015 to YLL], National Science Council [NSC 100-2314-B-400-002-MY3 to YLL] and the National Health Research Institutes, Taiwan [NP-105-PP-04, NP-106-PP-06, NP-105-SP-04 and NP-106-SP-04 to YLL]. This study was also supported in part by the National Heath Research Institutes and Central Government S&T Grant 106-1901-01-10-02 to YW and Ministry of Science and Technology of Taiwan MOST 106-2320-B-400-012 to YLL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.