Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use

Abstract

Methadone is a synthetic opioid used as maintenance treatment for patients addicted to heroin. Skin irritation is one of the adverse events caused by opioid use. 344 methadone maintenance treatment (MMT) patients were recruited with records and measurements on methadone dose, plasma methadone concentrations, and treatment emergent symptom scales (TESS). 15 patients reported with skin irritation. Five SNPs located within the NEC-TIN4 genetic region were genotyped. The NECTIN4 gene within the adherens junction interaction pathway was associated with methadone dose in pathway-based genome wide association analyses (P = 0.0008). Three highly-linked SNPs, rs11265549, rs3820097, and rs4656978, were significantly associated with methadone dose (P = 0.0003), plasma concentrations of R,S-methadone (P = 0.0004) and TNF-α (P = 0.010) in all 344 MMT patients, and with self-report skin irritation symptom scores (P = 0.010) in the 15 MMT patients who reported with skin irritation. To identify the possible roles of plasma level of Nectin-4 in the responses to MMT and opioid use, additional age-and gender-matched 51 controls and 83 methadone-free abstinent former heroin users were recruited. Plasma level of Nectin-4 was the highest in MMT patients among the three groups. The results suggest involvement of genetic variants on NECTIN4 in methadone dose. Plasma Nectin-4 level is likely an indicator for continued use of opioids.

Therapeutic prospects of nectin-4 in cancer: applications and value

“…As well as these potential applications in cancer diagnosis, increased levels of soluble Nectin-4 in serum may contribute to the diagnosis and monitoring of asthma ( 62 ) and may also represent a new biomarker for opioid dependence ( 63 , 64 ). To date, most research has focused on Nectin-4 as a transmembrane protein of tumor cells, with less attention paid to soluble Nectin-4.…”

Genetic implications in quality palliative care and preventing opioid crisis in cancer‐related pain management

“…Both opioid sensitivity and addiction warrant more attention to predict the increased risk of developing maladaptive patterns of opioid use (Table 1; Haufroid & Hantoson, 2015). Other GWAS and candidate gene studies found several other genetic variations possibly associated with phenotypes related to opioid sensitivity or addiction within/around gene regions, such as MCOLN1, PNPLA6, DDX18, PTPRD, MYOM2, SNAP25-AS1, NECTIN4, GRK5, and MYOCD (Table 1; Cheng et al, 2020;Cox et al, 2020;Fang et al, 2020;Nielsen et al, 2008;Wang et al, 2018). However, additional genetic research is needed on these important phenotypes that are of paramount clinical importance.…”

The Association between a MAOB Variable Number Tandem Repeat Polymorphism and Cocaine and Opiate Addictions in Polyconsumers

“…There is solid evidence of the role that genetic factors play in the development of addictive disorders [6][7][8]. Recent studies using GWAS (Genome-wide association study) have identified several novel genes that are associated with cocaine and opioid use [9][10][11]. Marees et al, (2020) found 2976 novel candidate genetic loci for substance use traits, and identified genes and tissues through which these loci potentially exert their effects [12].…”