Polymorphism of COMT Val158Met is associated with inhalant use and dependence: a Thai substance dependence treatment cohort

Background: Inhalants are abused by adolescents worldwide, but genetic markers of inhalant use or dependence are poorly understood.

Objective: We assessed the frequency and association of a functional polymorphism in the gene encoding catechol-O-methyltransferase (COMT Val158Met) in inhalant-dependent (ID) subjects and inhalant users (IU).

Methods: Demographic and diagnostic data were collected by interviewing 456 Thai-speaking methamphetamine (MA) users by using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). COMT Val158Met (rs4680) genotyping was acquired by restriction fragment length polymorphism. Individuals with ID or IU were compared with non-ID or non-IU by using a χ² test. After that, factors associated with ID or IU were analyzed by logistic regression. Blood samples from 217 healthy blood donors were used as controls for ID and IU in the allele frequency comparison. Deviation from Hardy-Weinberg Equilibrium Expectations (HWEE) was also tested.

Results: Out of 456 MA users, deviation from HWEE was observed in IU but not in ID, non-ID or from the total sample. The “Met” allele was significantly associated with ID (p = 0.02) and IU (p = 0.002) among MA users, but not in allele frequency comparisons when compared to the healthy control group (p > 0.1). With respect to logistic regression analysis, homo or heterozygosity for the “Met” allele, male sex, younger age, lower level of education, a major depressive episode (MDE), and alcohol dependence were associated with ID. Analyses of IU vs. non-IU yielded the same results except for age and MDE. In addition, individuals with MA-induced paranoia (MIP) were more likely to have used inhalants at least once in their lifetime compared to those without.

Conclusion: COMT 158Met, male sex, younger age, lower level of education, MDE, MIP, and alcohol dependence increased risk for inhalant use and/or dependence.