Mahla Asghari1, Soheila Abedini1, Sohrab Saghafi Khadem2, Amir Tajbakhsh3,1, Maliheh Alimardani1, Abolfazl Nesaei Bajestani4, Forough Alipoor5, Maryam Alidoust1, Amir Savardashtaki6,7, Peyman Hashemian8,9, Alireza Pasdar10,11,12. 1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Ibn-E-Sina and Dr Hejazi Psychiatry Hospital, University of Medical Sciences, Mashhad, Iran. 3. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Department of Medical Genetics, Ayatollah Madani Hospital, Gonabad University of Medical Sciences, Gonabad, Iran. 5. Islamic Azad University Torbat-e Jam Branch, Torbat-e-Jam, Iran. 6. Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 7. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. 8. Medical Genetics Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran. HashemianP@mums.ac.ir. 9. Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. HashemianP@mums.ac.ir. 10. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. PasdarA@mums.ac.ir. 11. Medical Genetics Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran. PasdarA@mums.ac.ir. 12. Division of Applied Medicine, Faculty of Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK. PasdarA@mums.ac.ir.
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.
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.
Entities:
Keywords:
Addiction; And polymorphisms; Dopamine pathway; Drug abuse; Glutamate pathway; Substance dependence; Substance use disorder (SUD); Variations
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