Blum Kenneth, Bowirrat Abdala, Elman Igor, Baron David, Thanos Panayotis K, Gold Mark S, Hanna Colin, Makale Milan T, Sunder Keerthy, Jafari Nicole, Zeine Foojan, Murphy Kevin T, Makale Miles, Badgaiyan Rajendra D
Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
Division of Addiction Research & Education, Center for Exercise Sports, Mental Health, Western University Health Sciences, Pomona, CA, USA.
Clin Exp Psychol. 2023 Jun 29;9(4):8-11.
Since 1990, published addiction psychiatry articles have exceeded 11,495. Several from Blum et al. showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum first published in JAMA (1990) concerning the association of the gene polymorphism and severe alcoholism, confirmation has been mixed and controversial. More recently, however, a meta-analysis of 62 studies showed a significant association between rs 1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al. 1990; a significant association between the minor allele, Taq A1 (rs 1800497 C>T) and severe alcoholism. Additionally, the rs1800497 is associated with suicide behaviors robustly at P=1.77 × 10. Furthermore, DNA polymorphic alleles underlying SUD with multiple substances were mapped via chromatin refolding, revealed that the gene and associated polymorphism(s) was the top gene signal (DRD2, P=7.9 × 10). Additionally, based on these investigations, we conclude that GWAS should end the controversy about the gene being at least one determinant of Reward Deficiency Syndrome (RDS) first reported in the Royal Society of Medicine journaling 1996.
自1990年以来，已发表的成瘾精神病学文章超过11495篇。布卢姆等人的几篇文章显示了遗传成瘾风险严重程度（GARS）测试在识别多物质和疼痛诊所、术后减肥手术患者以及面临监禁的酒驾罪犯群体中奖励缺乏行为风险方面的临床相关性。自从布卢姆于1990年首次在《美国医学会杂志》上发表关于基因多态性与严重酒精中毒关联的文章以来，相关的证实情况不一且存在争议。然而，最近一项对62项研究的荟萃分析显示，rs1800497与酒精使用障碍（AUD）之间存在显著关联。耶鲁大学的其他研究表明，基因A1等位基因的一个单倍型块与AUD和海洛因依赖有关。对120万退伍军人的抑郁症和自杀的全基因组关联研究（GWAS）证实了布卢姆等人在1990年首次发现的精神病候选基因研究结果；次要等位基因Taq A1（rs1800497 C>T）与严重酒精中毒之间存在显著关联。此外，rs1800497与自杀行为也有很强的关联，P值为1.77×10。此外，通过染色质重折叠对多种物质所致物质使用障碍（SUD）潜在的DNA多态性等位基因进行了定位，结果显示该基因及相关多态性是最强的基因信号（DRD2，P=7.9×10）。此外，基于这些研究，我们得出结论，GWAS应该结束关于该基因至少是1996年在《皇家医学学会杂志》上首次报道的奖励缺乏综合征（RDS）的一个决定因素的争议。
