Jiang Zhao, Zhang Tianxiao, Han Wei, Xiao Jing, Zhang Wenpei, Wang Xiaochen, Liu Jianing, Yang Ying, Yang Congying, Guan Fanglin, Li Tao, Rice John P
Department of Forensic Medicine, School of Medicine and Forensics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Key Laboratory of National Health Commission for Forensic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Front Pharmacol. 2023 Jul 6;14:1217382. doi: 10.3389/fphar.2023.1217382. eCollection 2023.
Methamphetamine use disorder (MUD) has become a global problem due to the highly addictive nature of methamphetamine. Earlier research have demonstrated that PROK2 functions as a compensatory and protective response against neurotoxic stress by stimulating astrocyte reactivity. The aim of our study was to evaluate the correlation between the gene and both MUD risk susceptibility and craving scale in the Chinese Han population. A total of 5,282 participants (1,796 MUD patients and 3,486 controls) were recruited. Seven tag SNPs of the gene were chosen and genotyped in the samples. Genetic association analyses were performed to capture the significant SNPs. To investigate the relationship between PROK2 levels and craving scores with the associated-SNP genotypes, we conducted a linear model. SNP rs75433452 was significantly linked with MUD risk (-value = 1.54 × 10), with the A allele being positively correlated with an increased risk of MUD. Moreover, the average serum level of PROK2 decreased when more copies of the A allele were presented in both MUD patients (-value = 4.57 × 10) and controls (-value = 1.13 × 10). Furthermore, the genotypes of SNP rs75433452 were strongly correlated with the craving scores in MUD patients (-value = 4.05 × 10). Our study identified a significant association signal of the gene with MUD risk susceptibility and methamphetamine craving scores in the Chinese Han population, providing potential valuable insights into the underlying mechanisms of METH dependence.
由于甲基苯丙胺具有高度成瘾性，甲基苯丙胺使用障碍（MUD）已成为一个全球性问题。早期研究表明，PROK2通过刺激星形胶质细胞反应性，发挥对神经毒性应激的代偿性和保护性反应作用。我们研究的目的是评估该基因与中国汉族人群中MUD风险易感性和渴求量表之间的相关性。共招募了5282名参与者（1796名MUD患者和3486名对照）。选择该基因的7个标签单核苷酸多态性（tag SNPs）并在样本中进行基因分型。进行遗传关联分析以找出显著的单核苷酸多态性。为了研究PROK2水平和渴求分数与相关单核苷酸多态性基因型之间的关系，我们进行了线性模型分析。单核苷酸多态性rs75433452与MUD风险显著相关（P值 = 1.54 × 10），A等位基因与MUD风险增加呈正相关。此外，在MUD患者（P值 = 4.57 × 10）和对照（P值 = 1.13 × 10）中，当出现更多拷贝的A等位基因时，PROK2的平均血清水平均下降。此外，单核苷酸多态性rs75433452的基因型与MUD患者的渴求分数密切相关（P值 = 4.05 × 10）。我们的研究在中国汉族人群中确定了该基因与MUD风险易感性和甲基苯丙胺渴求分数之间的显著关联信号，为甲基苯丙胺依赖的潜在机制提供了有价值的见解。
