Sains Malaysiana 52(11)(2023): 3211-3222

http://doi.org/10.17576/jsm-2023-5211-14

Association Analysis of a GSTP1 Functional Polymorphism with Methamphetamine Dependence and Associated Symptoms in a Multiethnic Malaysian Population

(Analisis Perkaitan Polimorfisme Fungsian GSTP1 dengan Pergantungan Metamfetamine dan Gejala Berkaitan dalam Populasi Berbilang Etnik di Malaysia)

HASIF ADLI ZAKARIAH¹, NIK NUR SYAHEERAH NIK ABDUL RAHMAN¹, WU YUAN SENG², SUZAILY WAHAB⁴ RUSDI ABDUL RASHID³ & SIM MAW SHIN^1,*

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

²Department of Biological Sciences, School of Medicine and Life Sciences, Sunway University, 47500 Petaling Jaya, Selangor, Malaysia

³Department of Psychological Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

⁴Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia,56000 Cheras, Kuala Lumpur, Malaysia

Received: 19 June 2023/Accepted: 2 November 2023

Abstract

Methamphetamine (METH) is a psychostimulant that is highly addictive and has been widely linked to the adverse effect on brain. METH-induced oxidative stress can be effectively protected by glutathione S-transferases (GSTs). Genetic polymorphism of GST gene family may affect the susceptibility of METH users to its dependence and associated symptoms. Therefore, this study investigated the association of a functional single nucleotide polymorphism rs1695 of GSTP1 gene with METH-induced symptoms and dependence in a Malaysian population, including Malay, Chinese, Kadazan-Dusun, and Bajau ethnic groups. Genotyping for GSTP1 rs1695 polymorphism from 230 METH-dependent male subjects and 232 healthy male controls was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). For statistical analyses, the χ² test and Fisher’s were performed in this research. The results showed a significant difference between GSTP1 rs1695 polymorphism and METH dependence in the Malay and Chinese populations. Our findings suggest that the GSTP1 rs1695 polymorphism may have possibility to methamphetamine dependence in the Malay and Chinese populations but not in other ethnicities. Furthermore, the Malay ethnic group who carried the -105G allele might have a protective role for METH-induced mania.

Keywords: GSTP1; methamphetamine; polymorphism; psychosis; stimulant

Abstrak

Metamfetamine (METH) ialah psikoperangsang yang sangat ketagihan dan telah dikaitkan secara meluas dengan kesan buruk kepada otak. Tekanan oksidatif aruhan METH boleh dilindungi dengan berkesan oleh glutation S-transferases (GST). Polimorfisme genetik gen famili GST boleh menjejaskan kerentanan pengguna METH kepada pergantungan dan gejala yang berkaitan. Oleh itu, penyelidikan ini mengkaji perkaitan polimorfisme fungsian nukleotida tunggal rs1695 gen GSTP1 dengan gejala dan pergantungan aruhan METH dalam populasi Malaysia, termasuk kumpulan etnik Melayu, Cina, Kadazan-Dusun dan Bajau. Penjenisan gen untuk polimorfisme GSTP1 rs1695 daripada 230 subjek lelaki pergantungan METH dan 232 lelaki sihat untuk kawalan telah dijalankan menggunakan polimorfisme panjang serpihan tindak balas rantai polimerase (PCR-RLFP). Untuk analisis statistik, ujianχ² dan Fisher telah dijalankan dalam penyelidikan ini. Keputusan menunjukkan perbezaan yang signifikan antara polimorfisme GSTP1 rs1695 dan pergantungan METH dalam populasi Melayu dan Cina. Penemuan kami mencadangkan bahawa polimorfisme GSTP1 rs1695 mungkin mempunyai kemungkinan pergantungan methamphetamine dalam populasi Melayu dan Cina tetapi tidak dalam etnik lain. Tambahan pula, kumpulan etnik Melayu yang membawa alel -105G mungkin mempunyai peranan perlindungan untuk aruhan METH mania.

Kata kunci: GSTP1; metamfetamine; perangsang; polimorfisme; psikosis

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*Corresponding author; email: garethsim@um.edu.my