Role of novelty seeking personality traits as mediator of the association between COMT and onset age of drug use in Chinese heroin dependent patients

Abstract

Background: Personality traits such as novelty seeking (NS) are associated with substance dependence but the mechanism underlying this association remains uncertain. Previous studies have focused on the role of the dopamine pathway.

Objective: Examine the relationships between allelic variants of the catechol-O-methyltransferase (COMT) gene, NS personality traits, and age of onset of drug use in heroin-dependent subjects in China.

Methods: The 478 heroin dependent subjects from four drug rehabilitation centers in Shanghai who were genotyped for eight tagging single nucleotide polymorphisms (SNP) on the COMT gene completed the NS subscale from the Temperament and Character Inventory. Multivariate analyses were used to assess the potential mediating role of NS personality traits in the association between COMT gene variants and the age of onset of heroin use.

Principal findings and conclusions: In the univariate analysis the COMT rs737866 gene variants were independently associated with both NS and age of onset of drug use: those with the TT genotype had higher NS subscale scores and an earlier onset age of heroin use than individuals with CT or CC genotypes. In the multivariate analysis the inclusion of the NS subscore variable weakened the relationship between the COMT rs737866 TT genotype and an earlier age of onset of drug use. Our findings that COMT is associated with both NS personality traits and with the age of onset of heroin use helps to clarify the complex relationship between genetic and psychological factors in the development of substance abuse.

Figure 1. Human COMT gene structure and location of eight tagging SNPs.

[The gray boxes and the white boxes indicate the exons of the COMT gene. The arrows indicate the location of each tagging SNPs.]

Figure 2. Linkage disequilibrium (LD) plot of the tagging eight SNPs.