Linkage disequilibrium and association with methamphetamine dependence/psychosis of μ-opioid receptor gene polymorphisms

Abstract

Several studies indicate that the m-opioid receptor plays a role in addiction not only to opiate drugs but also to alcohol and non-opiate addictive drugs. Our studies aim to reveal the associations between gene polymorphisms and methamphetamine (MAP) dependence/psychosis. We newly identified several polymorphisms and four substantial linkage disequilibrium (LD) blocks in the m-opioid receptor (OPRM1) gene. We found significant differences in both genotype and allele frequencies of the single-nucleotide polymorphism (SNP) IVS2 þ G691C between control (n ¼ 232) and MAPdependent/psychotic patients (n ¼ 128). There was also a significant association between IVS2 þ G691C and patients with transient psychosis. These results suggest that the OPRM1 gene variations may be a factor in development and prognosis of MAP psychosis.

Genetic factors involved in risk for methamphetamine intake and sensitization

“…With regard to the Chr 10 QTL region, the genes that we have found to be DE in one or more of the 3 brain regions include, Oprm1, Esr1 (estrogen receptor 1), pcmt1 (protein-L-isoaspartate [D-aspartate] O-methyltransferase 1), ppil4 (peptidylprolyl isomerase [cyclophilin]-like 4), Hivep2 (human immunodeficiency virus type 1 enhancer binding protein 2) , Nhsl1 (NHS-like 1), Pex7 (peroxisome biogenesis factor 7), Map3k5 (mitogen activated protein kinase kinase kinase 5), Amd1 (S-adenosylmethionine decarboxylase 1), Cirbp (cold inducible RNA binding protein), Rfx4 (regulatory factor S, 4), Dmt2 (dorso-medial telencephalon gene 2) and Fgd6 (FYVE, RhoGEF and PH domain containing 6). Partly because good pharmacological tools exist to manipulate mu opioid receptors, but also because several polymorphisms and linkage disequilibrium blocks in human OPRM1 have been associated with MA dependence/psychosis (Ide et al, 2006) and because buprenorphine, a mu-opioid receptor partial agonist, attenuated the effects of MA on dopaminergic neuro-transmission in rats (Pereira et al, 2011), we have pursued a line of research that has demonstrated highly significant differences between MALDR and MAHDR mice in both opioid sensitivity (Eastwood and Phillips, 2013) and intake (Eastwood and Phillips, submitted). However, any of the genes in the QTL region could be relevant.…”

“…Several genetic association studies have focused on specific genes; e.g., Oprm1 (Ide et al, 2006). Bousman et al (2009) reviewed the genetic association studies for MA use disorders and noted that 18 genes within 38 studies identified significant associations.…”

Association between Single Nucleotide Polymorphisms in the OPRM1 Gene and Intraoperative Remifentanil Consumption in Northern Chinese Women

“…Previous pharmacogenetic studies of SNP rs2075572 have shown varying results. A Japanese study found no association of the G allele of this SNP with postoperative analgesic requirements, but found an association with increased risk of methamphetamine dependence and psychosis [3,25] . A Chinese study found no association between rs2075572 and subjective heroin-induced responses [22] .…”

Novel Linkage Disequilibrium of Single Nucleotide Polymorphisms in the Transcriptional Regulatory Region of .MU.-Opioid Receptor Gene in Japanese Population

“…SNPs frequencies of Japanese OPRM1 in regions other than in the transcript region were provided in a previous report. 12) In our study, 5 SNPs (Ϫ1748G/A, Ϫ1565T/C, Ϫ1045A/G, Ϫ172G/T, Ϫ38C/A) were detected in the transcriptional regulatory region. Frequently, DNA binding affinity to the transcription factor is influenced by base substitution in transcription factor binding region or its neighborhood.…”