{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:26:18Z","timestamp":1753892778635,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats: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 (<jats:italic>HDAC3<\/jats: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 <jats:italic>HDAC3<\/jats:italic> to the vulnerability to METH dependence in a Han Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats: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 \u00b1 3 kb regions of <jats:italic>HDAC3<\/jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The SNP rs14251 was identified as a significant association signal (\u03c7<jats:sup>2<\/jats:sup> = 9.84, <jats:italic>P<\/jats: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\u20131.43)]. The results of <jats:italic>in silico<\/jats:italic> analyses suggested that SNP rs14251 could be a potential eQTL signal for <jats:italic>FCHSD1<\/jats:italic>, <jats:italic>PCDHGB6<\/jats:italic>, and <jats:italic>RELL2<\/jats:italic>, but not for <jats:italic>HDAC3<\/jats:italic>, in various human tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2022.870322","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T05:42:19Z","timestamp":1653025339000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 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