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

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.

<p>CLDN8 promotes colorectal cancer cell proliferation, migration, and invasion by activating MAPK/ERK signaling</p>

“…Claudin 8 (CLDN8), which is located in the cell membrane, is a member of the CLDN superfamily that constitutes tight junctions 13,14. CLDN8 is overexpressed in several human cancer cell lines and plays a vital role in the progression of several human cancers, including prostate cancer, renal cell carcinoma, and osteosarcoma 13–23.…”

Florfenicol induced renal inflammatory response and apoptosis via cell adhesion molecules signaling pathway

“…The claudins ( CLDN ) family of cell adhesion molecules signaling pathway can participate in inflammatory reaction together with CXCL-10. CLDN family mainly plays an important role in controlling cell permeability and maintaining tissue homeostasis ( Liu et al, 2017 ). CLDN8 is mainly expressed in endothelial cells, and is highly expressed in renal tissues, with tightly connected physiological functions ( Liu et al, 2019 ).…”