Opioid system genes in alcoholism: A case–control study in Croatian population

Čupić, Barbara; Štefulj, Jasminka; Zapletal, Emilija; Matošić, Ana; Bordukalo-Niksic, Tatjana; Čičin‐Šain, Lipa; Gabrilovac, Jelka

doi:10.1016/j.npep.2013.08.002

Cited by 10 publications

(5 citation statements)

References 41 publications

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“…A multicenter study with a family‐based design suggested a significant association of OPRK1 SNP rs6473797 with alcohol dependence . However, other studies showed negative results for the genetic effect of OPRK1 in alcoholism, contrary to ours …”

Section: Discussioncontrasting

confidence: 84%

“…The rs1799971 variant of OPRM1 has been the most frequently studied SNP for its association with alcohol dependence, though results have been inconsistent. Certain studies reported a significant association between rs1799971 and alcohol dependence, while others reported no genetic effect for this SNP . The most recent meta‐analysis reviewing 17 case‐control studies including nine Caucasian studies (8026 patients in total) and eight Asian studies (1587 patients in total) concluded that rs1799971 exhibited no association with alcohol dependence in either ethnicity .…”

Section: Discussionmentioning

confidence: 99%

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Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population

et al. 2019

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AimsRecent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients.MethodsThree μ‐opioid receptor gene (OPRM1) variants and two κ‐opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls. We applied the Alcohol Use Disorders Identification Test (AUDIT), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Dependence Scale. AUD patients also completed the stop‐signal task, delay discounting task, balloon analogue risk task, and the Barratt Impulsiveness Scale version 11 (BIS‐11).ResultsNo significant differences in genotype distributions or haplotype frequencies were found between AUD patients and controls. However, OPRK1 SNP rs6473797 was significantly related to the severity of alcohol‐related symptoms as measured by AUDIT and OCDS and a haplotype containing rs6473797 was also related to OCDS scores in AUD patients. For other psychological traits, OPRM1 SNP rs495491 was significantly associated with scores on the motor subfactor of the BIS‐11.ConclusionGenetic variations in opioid receptors may contribute to symptom severity and impulsivity in AUD patients.

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Section: Discussioncontrasting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population

et al. 2019

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“…Leeman et al discussed in depth how various animal models can appropriately recapitulate human studies, and importantly, the authors highlight the role alcohol consumption and abstinence (as well as heavy drinking) can play in informing the human literature (Leeman et al 2010). In the human population, genetic variants in the KOR gene OPRK1 modulate alcohol consumption (Li & Zhang 2013, Wang et al 2014) (though note that this effect is not replicated in all populations; see (Cupic et al 2013)). KOR antagonists can prevent alcohol self-administration in alcohol preferring rat lines (Cashman & Azar 2014).…”

Section: Behaviormentioning

confidence: 99%

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

Crowley

Kash

2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

106

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Kappa opioid receptors (KORs) in the central nervous system have been known to be important regulators of a variety of psychiatry illnesses, including anxiety and addiction, but their precise involvement in these behaviors is complex and has yet to be fully elucidated. Here, we briefly review the pharmacology of KORs in the brain, including KOR's involvement in anxiety, depression, and alcohol addiction. We also review the known neuronal circuitry impacted by KOR signaling, and interactions with corticotrophin-releasing factor (CRF), another key peptide in anxiety-related illnesses, as well as the role of glucocorticoids. We suggest that KORs are a promising therapeutic target for a host of neuropsychiatric conditions.

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“…Owing to the biological functions of POMC, the associations of SNPs in the POMC gene with substance dependence, obesity, and the development of Parkinson's disease have been investigated (Cupic et al 2013;Du et al 2011;Graff et al 2013;Hayase et al 2002;Kuehnen et al 2012;Shadrina et al 2006;Ternouth et al 2011;Wang et al 2012;Zhang et al 2009). In this study, we found that haplotypes of the POMC gene were associated with remission status with antidepressant treatment in patients with MDD via the interaction with SLE.…”

Section: Discussionmentioning

confidence: 99%

The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events

et al. 2014

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Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene-environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P = 0.010-0.035). Although observations were limited in patients without SLE, a significant haplotype-SLE interaction was observed (P = 0.020). Additionally, at 1, 2, and 8 weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P = 0.003-0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P = 0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.

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Opioid system genes in alcoholism: A case–control study in Croatian population

Cited by 10 publications

References 41 publications

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events

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