SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

Author:

Yahya Dayang Nooreffazleen1,Guad Rhanye Mac2ORCID,Wu Yuan-Seng34ORCID,Gan Siew Hua5ORCID,Gopinath Subash C. B.678ORCID,Zakariah Hasif Adli1ORCID,Rashid Rusdi Abdul9,Sim Maw Shin1ORCID

Affiliation:

1. Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia

2. Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia

3. Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Malaysia

4. Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Malaysia

5. School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia

6. Faculty of Chemical Engineering and Technology, Universiti Malaysia Perlis, Arau 02600, Malaysia

7. Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar 01000, Malaysia

8. Micro System Technology, Centre of Excellence (CoE), Universiti Malaysia Perlis (UniMAP), Pauh Campus, Arau 02600, Malaysia

9. Department of Psychological Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia

Abstract

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype.

Funder

Research University Grant

Malaysian Brain, Mind and Neuroscience Research Foundation

Ministry of Higher Education Malaysia Long-term Research Grant Scheme

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

Reference28 articles.

1. United Nations Office on Drugs and Crime (2022, November 23). Synthetic Drugs in East and South-East Asia Trends and Patterns of Am-phetamine-Type Stimulants and New Psychoactive Substances. A Report from the Global SMART Programme March 2019. Available online: https://www.unodc.org/documents/southeastasiaandpacific/Publications/2019/2019_The_Challenge_of_Synthetic_Drugs_in_East_and_SEA.pdf.

2. National Anti-Drugs Agency Malaysia (2022, November 23). Drug Statistics, Available online: https://www.adk.gov.my/en/public/drugs-statistics/.

3. United Nations Office on Drugs and Crime (2022, November 23). Methamphetamine Continues to Dominate Synthetic Drug Markets, Global SMART Update Volume 20. Available online: https://www.unodc.org/documents/scientific/Global_Smart_Update_20_web.pdf.

4. National Center for Biotechnology Information (2022, November 23). SLC1A2 Solute Carrier Family 1 Member 2 [Homo Sapiens (Human)], Available online: https://www.ncbi.nlm.nih.gov/gene/6506.

5. The SLC1 high-affinity glutamate and neutral amino acid transporter family;Kanai;Mol. Asp. Med.,2013

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