RGD Reference Report - Haplotype-Based Association and In Silico Studies of OPRM1 Gene Variants with Susceptibility to Opioid Dependence Among Addicted Iranians Undergoing Methadone Treatment.

General

Haplotype-Based Association and In Silico Studies of OPRM1 Gene Variants with Susceptibility to Opioid Dependence Among Addicted Iranians Undergoing Methadone Treatment.
Authors:	Tolami, Hedyeh Fazel Sharafshah, Alireza Tolami, Laleh Fazel Keshavarz, Parvaneh
Citation:	Tolami HF, etal., J Mol Neurosci. 2020 Apr;70(4):504-513. doi: 10.1007/s12031-019-01443-4. Epub 2019 Dec 18.
RGD ID:	401827954
Pubmed:	PMID:31853823 (View Abstract at PubMed)
DOI:	DOI:10.1007/s12031-019-01443-4 (Journal Full-text)
The associations of OPRM1 gene variants with opioid dependence have been demonstrated. This study investigated the association of rs495491, rs1799971 (A118G), rs589046, and rs10457090 variants of OPRM1 gene with opium dependence and their haplotypes among addicted individuals undergoing methadone treatment. Moreover, we investigated whether any of these variants were associated with libido dysfunction or insomnia among addicted people. A total of 404 individuals were genotyped by amplification refractory mutation system (ARMS) PCR. In silico studies were designed through homology modeling of A118G structures (N40 and D40) and docked with 41 FDA-approved drugs of OPRM1 protein by SWISS-MODEL, COACH, MolProbity, ProSA, Errat, Glide XP, and Autodock 4. Results revealed that rs495491, A118G, rs589046, and rs10457090 were significantly associated with opium dependence under recessive (P = 6.66E-10), dominant (P = 0.017), co-dominant (P = 0.001), and recessive (P = 9.28E-6) models of inheritance, respectively. Further analyses indicated three significant haplotypes including A-A-A-C (P-permutation < 1E-9), G-G-A-C (P-permutation = 0.04), and G-A-G-C (P-permutation = 8.69E-4). Genotype-phenotype associations of OPRM1 variants with insomnia and libido dysfunction showed no significant association. Docking showed the higher binding affinity of N40 rather than D40 model; however, methadone and morphine were bonded with D40 structure more powerful. Consequently, rs495491, A118G, rs589046, and rs10457090 were associated with opioid dependence among Iranians; also, A118G might be the most remarkable marker of OPRM1 owing to its vital structural roles.

Annotation Click to see Annotation Detail View

RGD Manual Disease Annotations Click to see Annotation Detail View

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
OPRM1	Human	opiate dependence		IAGP		DNA:SNPs: :multiple	RGD
Oprm1	Rat	opiate dependence		ISO	OPRM1 (Homo sapiens)	DNA:SNPs: :multiple	RGD
Oprm1	Mouse	opiate dependence		ISO	OPRM1 (Homo sapiens)	DNA:SNPs: :multiple	RGD

Objects Annotated

Genes (Rattus norvegicus)

Oprm1 (opioid receptor, mu 1)

Genes (Mus musculus)

Oprm1 (opioid receptor, mu 1)

Genes (Homo sapiens)

OPRM1 (opioid receptor mu 1)

Additional Information

Gene Annotator (Functional Annotation) unavailable	Gene Annotator (Annotation Distribution) unavailable	Variant Visualizer (Genomic Variants) unavailble Variant Visualizer (Genomic Variants) unavailable
Gene Annotator (Functional Annotation)	Gene Annotator (Annotation Distribution)	Variant Visualizer (Genomic Variants)

InterViewer (Protein-Protein Interactions) unavailable	Gviewer (Genome Viewer) unavailable	Variant Visualizer (Damaging Variants) unavailble Variant Visualizer (Damaging Variants) unavailable
InterViewer (Protein-Protein Interactions)	GViewer (Genome Viewer)	Variant Visualizer (Damaging Variants)

Gene Annotator (Annotation Comparison) unavailable	OLGA (Gene List Generator) unavailable
Gene Annotator (Annotation Comparison)	OLGA (Gene List Generator)	Excel (Download)

MOET (Multi-Ontology Enrichement) unavailable	GOLF (Gene-Ortholog Location Finder) unavailable
MOET (Multi-Ontology Enrichement)	GOLF (Gene-Ortholog Location Finder)

Create Name:

Description:

Send us a Message

Haplotype-Based Association and In Silico Studies of OPRM1 Gene Variants with Susceptibility to Opioid Dependence Among Addicted Iranians Undergoing Methadone Treatment.