Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort

Vadim Yuferov,* Eduardo R Butelman,* Mary Jeanne Kreek Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA *These authors contributed equally to this work Background: Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbid...

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Autores principales:	Yuferov V, Butelman ER, Kreek MJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	cannabis gender prodynorphin gene polymorphism dimensional phenotype Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/42dd4694a66a4dffb0e735f7f82b500b
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spelling	oai:doaj.org-article:42dd4694a66a4dffb0e735f7f82b500b2021-12-02T04:03:25ZGender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort1178-2021https://doaj.org/article/42dd4694a66a4dffb0e735f7f82b500b2018-04-01T00:00:00Zhttps://www.dovepress.com/gender-specific-association-of-functional-prodynorphin-68-bp-repeats-w-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Vadim Yuferov,* Eduardo R Butelman,* Mary Jeanne Kreek Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA *These authors contributed equally to this work Background: Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. Methods: In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp (PDYN 68 bp) promoter repeats with categorical diagnoses of cannabis dependence (Diagnostic and Statistical Manual of Mental Disorders-IV criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek–McHugh–Schluger–Kellogg cannabis scale). Results: The PDYN 68 bp genotype (examined as short–short [SS], short–long [SL], or long–long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis (p<0.05) and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p<0.045). Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group (p<0.045). Of interest, none of the aforementioned genetic associations were significant in females. Conclusion: This study provides the first data on how the PDYN 68 bp genotype is associated with gender-specific patterns of exposure to cannabis. Overall, this study shows that PDYN 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities. Keywords: cannabis, gender, prodynorphin, gene polymorphism, dimensional phenotypeYuferov VButelman ERKreek MJDove Medical Pressarticlecannabisgenderprodynorphingene polymorphismdimensional phenotypeNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 1025-1034 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cannabis gender prodynorphin gene polymorphism dimensional phenotype Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	cannabis gender prodynorphin gene polymorphism dimensional phenotype Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Yuferov V Butelman ER Kreek MJ Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
description	Vadim Yuferov,* Eduardo R Butelman,* Mary Jeanne Kreek Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA *These authors contributed equally to this work Background: Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. Methods: In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp (PDYN 68 bp) promoter repeats with categorical diagnoses of cannabis dependence (Diagnostic and Statistical Manual of Mental Disorders-IV criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek–McHugh–Schluger–Kellogg cannabis scale). Results: The PDYN 68 bp genotype (examined as short–short [SS], short–long [SL], or long–long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis (p<0.05) and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p<0.045). Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group (p<0.045). Of interest, none of the aforementioned genetic associations were significant in females. Conclusion: This study provides the first data on how the PDYN 68 bp genotype is associated with gender-specific patterns of exposure to cannabis. Overall, this study shows that PDYN 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities. Keywords: cannabis, gender, prodynorphin, gene polymorphism, dimensional phenotype
format	article
author	Yuferov V Butelman ER Kreek MJ
author_facet	Yuferov V Butelman ER Kreek MJ
author_sort	Yuferov V
title	Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
title_short	Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
title_full	Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
title_fullStr	Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
title_full_unstemmed	Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort
title_sort	gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an african american cohort
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/42dd4694a66a4dffb0e735f7f82b500b
work_keys_str_mv	AT yuferovv genderspecificassociationoffunctionalprodynorphin68bprepeatswithcannabisexposureinanafricanamericancohort AT butelmaner genderspecificassociationoffunctionalprodynorphin68bprepeatswithcannabisexposureinanafricanamericancohort AT kreekmj genderspecificassociationoffunctionalprodynorphin68bprepeatswithcannabisexposureinanafricanamericancohort
_version_	1718401426430885888

Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort

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