AUTHOR=Xiao Jing , Ma Yitian , Wang Xiaochen , Wang Changqing , Li Miao , Liu Haobiao , Han Wei , Wang Huiying , Zhang Wenpei , Wei Hang , Zhao Longrui , Zhang Tianxiao , Lin Huali , Guan Fanglin 

TITLE=The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3

JOURNAL=Frontiers in Psychiatry

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.870322

DOI=10.3389/fpsyt.2022.870322

ISSN=1664-0640

ABSTRACT=<sec><title>Objectives</title><p>Methamphetamine (METH) is a central nervous psychostimulant and one of the most frequently used illicit drugs. Numerous genetic loci that influence complex traits, including alcohol abuse, have been discovered; however, genetic analyses for METH dependence remain limited. An increased histone deacetylase 3 (<italic>HDAC3</italic>) expression has been detected in Fos-positive neurons in the dorsomedial striatum following withdrawal after METH self-administration. Herein, we aimed to systematically investigate the contribution of <italic>HDAC3</italic> to the vulnerability to METH dependence in a Han Chinese population.</p></sec><sec><title>Methods</title><p>In total, we recruited 1,221 patients with METH dependence and 2,328 age- and gender-matched controls. For genotyping, we selected 14 single nucleotide polymorphisms (SNPs) located within ± 3 kb regions of <italic>HDAC3</italic>. The associations between genotyped genetic polymorphisms and the vulnerability to METH dependence were examined by single marker- and haplotype-based methods using PLINK. The effects of expression quantitative trait loci (eQTLs) on targeted gene expressions were investigated using the Genotype-Tissue Expression (GTEx) database.</p></sec><sec><title>Results</title><p>The SNP rs14251 was identified as a significant association signal (χ<sup>2</sup> = 9.84, <italic>P</italic> = 0.0017). An increased risk of METH dependence was associated with the A allele (minor allele) of rs14251 [odds ratio (95% CI) = 1.25 (1.09–1.43)]. The results of <italic>in silico</italic> analyses suggested that SNP rs14251 could be a potential eQTL signal for <italic>FCHSD1</italic>, <italic>PCDHGB6</italic>, and <italic>RELL2</italic>, but not for <italic>HDAC3</italic>, in various human tissues.</p></sec><sec><title>Conclusion</title><p>We demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.</p></sec>