Association of PICK1 and BDNF variations with increased risk of methamphetamine dependence among Iranian population: a case–control study

Abstract

Abstract Background Genetic factors play an important role in susceptibility to methamphetamine dependency. In this line, protein that interact with C-kinase-1 (PICK1) and brain-derived neurotrophic factor (BDNF) genes are linked to methamphetamine dependence (substance use disorder). Thus, in a case–control study, we investigated the association between polymorphisms of PICK1 and BDNF genes and methamphetamine dependence in an Iranian population. Methods Total of 235 cases and 204 controls were recruited in a period between 2015 to 2018. The PICK1-rs713729, -rs2076369 and BDNF-rs6265 genotypes were determined via ARMS-PCR assay. Statistical analysis was performed, using SPSS 20.0, PHASE 2.1.1 program as well as SNP Analyzer 2.0. Results In the present study, two polymorphisms including PICK1-rs713729 (OR 1.38 (CI 1.08–1.52; P-value 0.004) in multiplicative and dominant models, and PICK1-rs2076369 (OR 1.31 (CI 1.10–1.56; P-value 0.002) in multiplicative, dominant and co-dominant models were associated with the risk of methamphetamine abuse. Moreover, haplotype analysis showed a significant association of haplotype AG (OR 2.50 (CI 1.50–4.16; P-value 0.0002) in dominant, recessive and co-dominant models, and haplotype TT (OR 0.67 (CI 0.50–0.91; P-value 0.009) in dominant and co-dominant models with the risk of methamphetamine abuse. None of the polymorphisms in this study had a high level of linkage disequilibrium. Conclusion Our findings indicate that the PICK1 gene polymorphism might affect the risk of methamphetamine dependency in our population.

Keywords

• Addiction
• Drug abuse
• Substance dependence
• Substance use disorder (SUD)
• Dopamine pathway
• Glutamate pathway