Do NeuroD Gene Polymorphisms Predict the Risk of Heroin Dependence or Mediate the Association between Personality Traits and Heroin Dependence?

Abstract

Objective: Heroin dependence (HD) affects brain development and is known to be heritable. The NeuroD gene encodes a neuroge nic differentiation factor, and its expression is essential for the development of the central nervous system. In this genetic case-control study, we aimed to investigate whether NeuroD gene polymorphisms associate with the occurrence of HD and the specific personality traits of patients with HD. Methods: 1107 unrelated participants (584 patients with HD and 523 controls) were recruited to the study The patients with HD were classified into six clinical subgroups based on their gender, duration, and age of onset to reduce heterogeneity. In total, 539 subjects completed the personality trait assessments. Results: We found a weak association between the NeuroD 1 rs16867467 locus and HD (p=0.048); this weak association was found only in the male (p=0.039) and late onset (p=0.047) HD subgroups. These findings could not be confirmed after haplotype analysis and Bonferroni corrections for multiple comparisons. Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. However, none of the polymorphisms in the NeuroD gene affected the NS and HA scores in both patients and healthy subjects (p>0.05). A negative correlation was found between age and novelty seeking scores in both groups, suggesting novelty seeking personality trait as a risk factor for early-onset HD. Conclusion: This study suggests that the NeuroD gene may neither contribute to the risk of HD nor mediate the relationship between specific personality traits and HD.