Relationship between Single Nucleotide Polymorphisms of GRHL3 and Schizophrenia Susceptibility: A Preliminary Case-Control Study and Bioinformatics Analysis

Sargazi, Saman; Heidari Nia, Milad; Sheervalilou, Roghayeh; Mirinejad, Shekoufeh; Harati-Sadegh, Mahdiyeh; Moudi, Mahdiyeh; Saravani, Ramin; Shakiba, Mansoor

doi:10.22088/IJMCM.BUMS.9.2.154

Volume 9, Issue 2 (Int J Mol Cell Med 2020) Int J Mol Cell Med 2020, 9(2): 154-164 | Back to browse issues page

‎ 10.22088/IJMCM.BUMS.9.2.154

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Sargazi S, Heidari Nia M, Sheervalilou R, Mirinejad S, Harati-Sadegh M, Moudi M, et al . Relationship between Single Nucleotide Polymorphisms of GRHL3 and Schizophrenia Susceptibility: A Preliminary Case-Control Study and Bioinformatics Analysis. Int J Mol Cell Med 2020; 9 (2) :154-164
URL: http://ijmcmed.org/article-1-1317-en.html

Relationship between Single Nucleotide Polymorphisms of GRHL3 and Schizophrenia Susceptibility: A Preliminary Case-Control Study and Bioinformatics Analysis

Saman Sargazi¹

, Milad Heidari Nia¹

, Roghayeh Sheervalilou¹

, Shekoufeh Mirinejad¹

, Mahdiyeh Harati-Sadegh²

, Mahdiyeh Moudi²

, Ramin Saravani³

, Mansoor Shakiba⁴

1- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
2- Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
3- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. , saravaniramin@yahoo.com
4- Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran; Psychosomatic Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Abstract: (4040 Views)

Grainyhead-like (GRHL) transcription factors were recently linked to the etiology of neural tube defects (NTDs). Overlapping patterns in the variation of schizophrenia (SCZ) incidence with that of NTDs suggests the presence of common etiological risk factors. This preliminary study was designed to examine the relationship between two missense variants of GRHL3 gene (rs2486668C/G and rs545809A/T) and SCZ susceptibility among Iranians. Three hundred ninety subjects (192 patients confirmed with SCZ, and 198 healthy controls) were enrolled and genotyped. Statistical and bioinformatics analyzes were performed to determine the effects of the variants. In silico analyzes were performed to determine the effects of the variants on the secondary structure of GRHL3 protein and prediction of silencer motifs for each variation. Statistically significant differences were observed between the studied groups under codominant AA, dominant AT+AA, and recessive AA genetic contrast models for rs545809A/T. The presence of the A allele of rs545809A/T enhanced SCZ risk by 2.33 fold. In contrast, rs2486668C/G was not linked to SCZ susceptibility (P > 0.05). Bioinformatics analysis revealed that both missense SNPs caused substantial changes in the secondary structure of GRHL3-mRNA. Screening of the ﬂanking sequences of rs545809A/T predicted silencer motifs for this SNP. Our results demonstrated that the rs545809A/T of GRHL3 gene could affect the risk of SCZ in Iranian populations. Replication studies are warranted to confirm these results.

Keywords: Bioinformatics, grainyhead-like 3, haplotype, polymorphism, schizophrenia

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Type of Study: Original Article | Subject: Genetics & Disease
Received: 2020/05/7 | Accepted: 2020/07/28 | Published: 2020/06/30