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rs1437396 基因多态性与酒精使用障碍及其合并重性抑郁障碍的相关性。

The association between the gene polymorphism at rs1437396 and alcohol use disorder, with or without major depression disorder.

机构信息

1Iuliu Hatieganu University of Medicine and Pharmacy, Department of Neurosciences - Psychiatry, Cluj-Napoca, Romania.

2Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.

出版信息

Arh Hig Rada Toksikol. 2023 Jun 26;74(2):127-133. doi: 10.2478/aiht-2023-74-3690. eCollection 2023 Jun 1.

Abstract

Girdin is a protein involved in neuronal migration and hippocampal development. It is encoded by the coiled-coil domain-containing 88A () gene, located on the short arm of chromosome 2 (2p). The gene is modulated by the intergenic single-nucleotide polymorphism (SNP) of the rs1437396, situated 9.5 kb downstream from its transcription stop site. As recent genome-wide research has associated the T allele of the SNP with increased risk of alcohol use disorder (AUD), we wanted to validate this finding in an independent cohort and to test further for an association with comorbid major depressive disorder (MDD). The study included 226 AUD patients (AUD group), 53 patients with comorbid MDD, and 391 controls selected randomly. The participants were genotyped for the rs1437396 polymorphism using the real-time polymerase chain reaction. The association between the rs1437396 polymorphism and increased risk of AUD and AUD+MDD was tested with logistic regression. Our results show significantly higher frequency of the T risk allele in the AUD group (p=0.027) and even higher in the AUD+MDD group (p=0.016). In conclusion, this is the first study that has validated the association between the rs1437396 polymorphism of the gene and AUD with or without MDD. Studies on larger samples of patients are needed to further investigate the mechanism of this association.

摘要

Girdin 是一种参与神经元迁移和海马体发育的蛋白质。它由卷曲螺旋结构域包含 88A(coiled-coil domain-containing 88A)基因编码,该基因位于 2 号染色体(2p)的短臂上。该基因受其转录终止位点下游 9.5 kb 处的基因间单核苷酸多态性(single-nucleotide polymorphism,SNP)rs1437396 的调控。最近的全基因组研究表明,SNP 的 T 等位基因与酒精使用障碍(alcohol use disorder,AUD)的风险增加相关,因此我们希望在独立队列中验证这一发现,并进一步测试其与共病重度抑郁症(major depressive disorder,MDD)的关联。该研究纳入了 226 名 AUD 患者(AUD 组)、53 名共病 MDD 患者和 391 名随机选择的对照者。使用实时聚合酶链反应(polymerase chain reaction,PCR)对 rs1437396 多态性进行基因分型。使用逻辑回归检验 rs1437396 多态性与 AUD 及 AUD+MDD 风险增加的相关性。我们的结果显示,AUD 组中 T 风险等位基因的频率显著更高(p=0.027),在 AUD+MDD 组中甚至更高(p=0.016)。总之,这是第一项验证 基因 rs1437396 多态性与 AUD 及 AUD+MDD 之间关联的研究。需要对更大样本的患者进行研究,以进一步探讨这种关联的机制。

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