GxE interaction effects of HCRTR2 single nucleotide polymorphism and adverse childhood experiences on methamphetamine use disorder

ABSTRACT

Background: Methamphetamine use disorder (MUD) is a worldwide health concern. The hypothalamic orexin system regulates stress response and addictive behaviors. The genetic variation in the hypocretin receptor 2 (HCRTR2), rs2653349, is associated with substance use disorder.

Objectives: We explored the gene-environment (GxE) interaction of rs2653349 and adverse childhood experiences (ACEs) associated with MUD susceptibility.

Methods: Four hundred and one individuals (336 males, 65 females) with MUD and 348 healthy controls (288 males, 60 females) completed a self-report questionnaire evaluating ACEs, encompassing childhood abuse and household dysfunction categories, and were genotyped for SNP rs2653349. Methamphetamine use variables were collected using the Diagnostic Interview for Genetic Studies. We used regression analyses to assess the GxE effect on MUD risk.

Results: The MUD group had a comparable genotypic distribution for rs2653349 to the control group, albeit with a higher prevalence and number of types of ACEs, correlating with an increased MUD risk (p < .05). No significant genetic impact of rs2653349 on MUD risk was found. However, we observed a GxE interaction effect between the minor allele of rs2653349 and the number of childhood abuse or household dysfunction types, correlating with a reduced MUD risk (OR = -0.71, p = .04, Benjamini-Hochberg adjusted p = .08 and OR = -0.59, p = .045, Benjamini-Hochberg adjusted p = .09, respectively).

Conclusion: HCRTR2 SNP rs2653349 has no significant impact on MUD risk, but ACEs may increase this risk. GxE results suggest that rs2653349 could offer protection against developing MUD in individuals experiencing multiple types of ACEs.

KEYWORDS:

• Methamphetamine use disorder
• orexin
• genetics
• adverse childhood experience
• gene-environment interaction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authorship contribution statement

Ming-Chyi Huang: conceptualized, designed, and conducted the study, critically revised the manuscript for important intellectual content; Kai-Ting Chen: reviewed the bulk of literature and wrote the first draft of the manuscript; Chun-Lin: recruited patients. Chung-Feng Kao analyzed the data and revised the manuscript; Hu-Ming Chang: incorporated edits from coauthors and assisted in data interpretation. All authors contributed to and have approved the final manuscript.

Ethical statement

This study was approved by the Institutional Review Board [TCPC; IRB No: 980405] of the Taipei City Psychiatric Center, Taipei City Hospital, and was in accordance with the Declaration of Helsinki. All participants provided written informed consent.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/00952990.2023.2297661.

Additional information

Funding

This study was supported by the National Science Council, Taiwan (NSC 97-2314-B-532-001-MY3; MOST 110-2314-B-532-005-MY3 [Ming- Chyi Huang]; NSTC 111-2314-B-532-008 [Hu-Ming Chang]); Taipei City Government (TPECH 11301-62-016 [Ming-Chyi Huang]; 11201-62-025 [Hu-Ming Chang]); Taipei City Hospital, Taiwan (TPCH 113-56 [Ming-Chyi Huang]).