Abstract

Purpose

Converging evidence has recently established the significance of γ-aminobutyric acid neurotransmitter (GABA) system in the development of schizophrenia (SCZ). We aimed to determine the association of two markers of the GABA_A receptor β₂ subunit gene (GABRB2), rs12187676 G/C and rs1816072 T/C, with the risk of SCZ in Iranian population.

Materials and methods

In this case-control study, 190 patients with SCZ and 200 healthy controls were recruited from December 2018 to February 2020. Genotyping was done using the Tetra-ARMS-PCR technique. In silico analyses were performed to determine the potential effects of the variants.

Results

The C allele and genotypes of codominant CC vs.TT and CT vs.TT, dominant TT vs. TC + CC, recessive TT + TC vs. CC of rs1816072 polymorphism, as well as codominant CC vs. GG and recessive GG + GC vs. CC genetic models of rs12187676 polymorphism were significantly associated with SCZ susceptibility. Compared to the TC/GC model, we have found that the TC/CC combination significantly increased the risk of SCZ by 4.32 fold while the TT/GG combination conferred a protective role against SCZ. Haplotypes analysis indicated that GABRB2 polymorphisms are in weak linkage disequilibrium with each other (LD = 0.1). However, bioinformatics analyses predicted that these polymorphisms do not have significant effects on the secondary structure and the splicing of GABRB2-mRNA.

Conclusions

We found that intronic GABRB2 polymorphisms were associated with SCZ risk in a sample of the Iranian population. These findings provided proof of concept for the involvement of the GABAergic neurotransmission system in SCZ development. These observations should be validated across other ethnicities and clinical subtypes.

中文翻译：

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GABRB2基因多态性与精神分裂症易感性的关系：病例对照研究和计算机分析

摘要

目的

最近，越来越多的证据证实了 γ-氨基丁酸神经递质 (GABA) 系统在精神分裂症 (SCZ) 发展中的重要性。我们旨在确定 GABA _A受体 β ₂亚基基因 ( GABRB2 ) 的两个标志物 rs12187676 G/C 和 rs1816072 T/C 与伊朗人群中 SCZ 风险的关联。

材料和方法

在这项病例对照研究中，从 2018 年 12 月至 2020 年 2 月招募了 190 名 SCZ 患者和 200 名健康对照。基因分型使用 Tetra-ARMS-PCR 技术进行。进行计算机分析以确定变体的潜在影响。

结果

rs1816072多态性的共显性CC vs.TT和CT vs.TT、显性TT vs. TC + CC、隐性TT + TC vs. CC的C等位基因和基因型，以及共显性CC vs. GG和隐性GG + GC vs. . rs12187676多态性的CC遗传模型与SCZ易感性显着相关。与 TC/GC 模型相比，我们发现 TC/CC 组合显着增加了 4.32 倍的 SCZ 风险，而 TT/GG 组合赋予了对 SCZ 的保护作用。单倍型分析表明GABRB2多态性之间存在弱连锁不平衡（LD = 0.1）。然而，生物信息学分析预测这些多态性对GABRB2 -mRNA的二级结构和剪接没有显着影响。

结论

我们发现内含子GABRB2多态性与伊朗人口样本中的 SCZ 风险相关。这些发现为 GABA 能神经传递系统参与 SCZ 发展提供了概念证明。这些观察结果应在其他种族和临床亚型中得到验证。