title: Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder.
abstract: Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders.
authors.affiliation: UCLA Department of Family Medicine and Center for Behavioral and Addiction Medicine, Los Angeles, CA, USA. Electronic address: kheinzerling@mednet.ucla.edu.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Heinzerling
authors.affiliation: UCLA Department of Statistics, Los Angeles, CA, USA.
authors.forename: Levon
authors.initials: L
authors.lastname: Demirdjian
authors.affiliation: UCLA Department of Statistics, Los Angeles, CA, USA.
authors.forename: Yingnian
authors.initials: Y
authors.lastname: Wu
authors.affiliation: UCLA Department of Family Medicine and Center for Behavioral and Addiction Medicine, Los Angeles, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Shoptaw
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D002140:California; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D044465:White People / Q000235:genetics
chemical_list: C115163:CREB1 protein, human; D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D008694:Methamphetamine
keywords: Ancestry; CREB1; Genetics; Methamphetamine; Pharmacotherapy; Sex