Associations between methamphetamine use disorder and , , , and gene sequence variants and expression levels.

INTRODUCTION

Assessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: and between controls and people with methamphetamine use disorder.

METHODS

Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. , and SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR.

RESULTS

Pro4Thr was associated with methamphetamine use disorder (OR = 6.22;  = .007). variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity ( = .003) and positively associated with inhibitory control performance ( = .006), respectively. Val66Met was associated with the severity of use ( = .008). and mRNA levels were lower in people who use methamphetamine relative to controls ( = .021 and .010, respectively).

CONCLUSIONS

is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood and mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.