The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR gene polymorphisms and borderline personality disorder in female heroin-dependent Chinese subjects

- Gene polymorphisms were selected from serotonergic and catecholaminergic systems.
- MAOA-LPR was associated with co-morbid BPD in female heroin-dependent patients.
- 5-HTTVNTR was associated with the co-morbidity of BPD and heroin-dependence.
- The interactions among MAOA-LPR, 5-HTTVNTR and rs6311 were close to significance.
- The interaction between MAOA-LPR and 5-HTTVNTR was also close to significance level.

ObjectiveTo explore the association between the 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with co-morbid borderline personality disorder (BPD) in female heroin-dependent patients.Subjects and methodsIn a case control study, we compared the polymorphic distributions of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 296 female heroin-dependent patients (including 61 patients with BPD and 235 without BPD) and 101 normal females by genotypes, alleles, and interaction between genes.ResultsFemale heroin-dependent subjects with BPD have lower frequency of the high activity allele (L: 4 repeats (4R)) of MAOA-LPR than those female heroin-dependent subjects without BPD, and have higher 5-HTTVNTR 10R/10R genotype frequency than normal female controls, with adjusted P-value < 0.05 (after adjusted for multiple testing by 1000-fold permutation tests) respectively. By MDR (Multifactor Dimensionality Reduction) analyses, the interactive effects between MAOA-LPR and 5-HTTVNTR, and among MAOA-LPR, 5-HTTVNTR and rs6311 were close to the significance level (P = 0.05) in predicting the risk of co-morbidity of BPD and heroin dependence relative to normal female controls, with 1000-fold permutation testing P-value < 0.06 however > 0.05 respectively.Conclusion5-HTTVNTR and MAOA-LPR may have independent predictive effects on co-morbid BPD in female heroin-dependent patients; the gene-gene interactions between MAOA-LPR and 5-HTTVNTR, and among MAOA-LPR, 5-HTTVNTR and rs6311 might also be involved in the etiology of this co-morbidity.