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Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice.

ABSTRACT: OPRM1 A118G, a functional human mu-opioid receptor (MOR) polymorphism, is associated with drug dependence and altered stress responsivity in humans as well as altered MOR signaling. MOR signaling can regulate many cellular processes, including gene expression, and many of the long-term, stable effects of drugs and stress may stem from changes in gene expression in diverse brain regions. A mouse model bearing an equivalent polymorphism (Oprm1 A112G) was previously generated and studied. Mice homozygous for the G112 allele show differences in opioid- and stress-related phenotypes.The current study examines the expression of 24 genes related to drug and stress responsivity in the caudoputamen, nucleus accumbens, hypothalamus, hippocampus, and amygdala of drug-naïve, stress-minimized, male and female mice homozygous for either the G112 variant allele or the wild-type A112 allele.We detected nominal genotype-dependent changes in gene expression of multiple genes. We also detected nominal sex-dependent as well as sex-by-genotype interaction effects on gene expression. Of these, four genotype-dependent differences survived correction for multiple testing: Avp and Gal in the hypothalamus and Oprl1 and Cnr1 in the hippocampus.Changes in the regulation of these genes by mu-opioid receptors encoded by the G112 allele may be involved in some of the behavioral and molecular consequences of this polymorphism observed in mice.

SUBMITTER: Collins D

PROVIDER: S-EPMC6132675 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice.

Collins Devon D Randesi Matthew M da Rosa Joel Correa JC Zhang Yong Y Kreek Mary Jeanne MJ

Psychopharmacology 20180719 9

<h4>Background</h4>OPRM1 A118G, a functional human mu-opioid receptor (MOR) polymorphism, is associated with drug dependence and altered stress responsivity in humans as well as altered MOR signaling. MOR signaling can regulate many cellular processes, including gene expression, and many of the long-term, stable effects of drugs and stress may stem from changes in gene expression in diverse brain regions. A mouse model bearing an equivalent polymorphism (Oprm1 A112G) was previously generated and ...[more]

PMID: 30027498

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Project description:Breast cancer is one of the most widespread malignancies in females, and the incidence rate has been increasing in recent years in the world. Genetic factors play an important role in the occurrence of breast cancer. Our study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of claudin 10 (CLDN10) (rs1325774, rs7333503, rs3751334) and breast cancer and the clinical characteristics of patients.A total of 104 patients with breast cancer and 118 healthy controls were recruited in our study between 2013 and 2015. The SNPscan system was used for genotyping. Demographic information, health status, anthropometric parameters and clinical data were considered in analysis. Statistical analysis of the data was carried out using the Student t test, the Chi-square test (X2) or Fisher exact test and unconditional logistic regression analysis. The Gene Expression Profiling Interactive Analyses application (GEPIA) was used to analysis the expression of CLDN10 in breast cancer tissues and normal samples.The polymorphism of rs1325774 was significantly associated with an increased risk of breast cancer (T/G vs T/T: OR?=?2.073, 95% CI?=?1.095-3.927, P?=?.025). After adjusting for age, the association remained statically significant (T/G vs T/T: OR?=?2.067, 95% CI?=?1.070-3.867, P?=?.026). Furthermore, harbouring G allele in rs1325774 position was significantly associated with increased risk of breast cancer (OR?=?1.993, 95% CI?=?1.107-3.589, P?=?.022). However, no significant association among rs7333503, rs3751334, and breast cancer. The expression level of CLDN10 was reduced in breast cancer tissues compared with normal breast tissues according to the analysis of The Cancer Genome Atlas (TCGA) data through GEPIA.Our results suggest that the polymorphism of rs1325774 associate with increase the breast cancer risk. No significant relationship between rs1325774 polymorphism and clinical as well as pathological characteristics in patients.

Dataset Information

Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice.

Publications

Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice.

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