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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.

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.
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Liu TH, Chung RH, Wang SC, Fang CP, Tsou HH, Shih CL, Kuo HW, Wang Y, Liu YL,


Liu TH, Chung RH, Wang SC, Fang CP, Tsou HH, Shih CL, Kuo HW, Wang Y, Liu YL, (click to view)

Liu TH, Chung RH, Wang SC, Fang CP, Tsou HH, Shih CL, Kuo HW, Wang Y, Liu YL,

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PloS one 2017 11 1612(11) e0187639 doi 10.1371/journal.pone.0187639

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 = 1.01×10-5), where the claudin 8 (CLDN8) gene had the most significant association (P = 6.8×10-5). 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.

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