Altered Levels of Basal Cortisol in Healthy Subjects with a 118G Allele in Exon 1 of the Mu Opioid Receptor Gene

Abstract

The mu opioid receptor is centrally involved in the development of the addictive diseases. It also modulates the stress responsive hypothalamic-pituitary-adrenal axis. Receptors encoded by the variant 118G polymorphism in exon 1 of the mu opioid receptor gene have a threefold increase in beta-endorphin binding and beta-endorphin is three times more potent in receptor-mediated activation of G protein-coupled inwardly rectifying potassium channels. Humans with this variant have increased stress response following opioid antagonism. Here, we study basal levels of adrenocorticotropic hormone and cortisol in subjects with this variant. In all, 59 healthy adults were genotyped and had morning levels of adrenocorticotropic hormone and cortisol measured following intravenous administration of saline placebo. Subjects with a 118G allele had significantly greater levels of cortisol than subjects with the prototype gene. Groups did not differ in levels of adrenocorticotropic hormone. A planned comparison revealed significantly greater cortisol in females with at least one copy of the 118G allele compared to females with the prototype gene. There was no significant effect of gender alone, nor was there a significant interaction between gender and genotype, on ACTH or cortisol. Subjects with at least one copy of the 118G allele have increased basal levels of cortisol, which may influence the susceptibility to and treatment of the stress responsive dyscrasia.

Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G

“…An elevated baseline is not a persistent characteristic of the GA/GG allele genotype; the female genotype groups exhibited no baseline differences during the placebo condition in the naltrexone protocol (Figure 2), as also found by others (Chong et al, 2008). Another group reported elevated cortisol secretion in AA women (Bart et al, 2006). The levels of cortisol output achieved by the women during the stress protocol (Figure 1) do not exhaust the response capacity of the HPA as indicated by the higher levels achieved following naltrexone administration (Figure 2).…”

Pain Intensity the First Year after Lumbar Disc Herniation Is Associated with the A118G Polymorphism in the Opioid Receptor Mu 1 Gene: Evidence of a Sex and Genotype Interaction

“…As presented in this study, women carrying the 118G allele had a mean VAS pain score 2.3 times higher than men with the same genotype 12 months after the lumbar disc herniation. Earlier data show that women carrying the 118G allele may have increased basal level of cortisol (Bart et al, 2006), consistent with a higher report of pain. Together these findings suggest that the high pain intensity in women compared with men in the low back pain and sciatic patients 12 months after the lumbar disc herniation may be related to the 118G substitution.…”

Subjective health complaints in patients with lumbar radicular pain and disc herniation are associated with a sex - OPRM1 A118G polymorphism interaction: a prospective 1-year observational study

“…Moreover, in one human experimental study, region-specific differences in OPRM1 levels between individuals with AA and G alleles have been demonstrated [34]. Additionally, the OPRM1 genotype may influence stress responses, immune and pro-inflammatory responses [21,35-37], and reactivity to social rejection [27]. Also, acute and chronic stress has been suggested to affect available μ-opioid receptor pools in GABAergic interneurons differentially in female and male rats [38].…”