Relationship between GABRB2 gene polymorphisms and schizophrenia susceptibility: a case-control study and in silico analyses

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.

Keywords:

• GABA receptor
• schizophrenia
• in silico
• single nucleotide polymorphism

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgment

The authors also wish to thank the staff psychiatric clinic at Baharan Hospital (Zahedan, Iran).

Additional information

Funding

This work was financially supported by the Cellular and Molecular Research Center of Zahedan University of Medical Sciences (Grant Number: 9024).