Association between polymorphisms in the GRIN1 gene 5' regulatory region and schizophrenia in a northern Han Chinese population and haplotype effects on protein expression in vitro.

Abstract

BACKGROUND:

Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia.

METHODS:

We conducted a case-control study to investigate the association between the GRIN1 gene, which encodes the NR1 subunit, and the risk of schizophrenia in a northern Chinese Han population using Sanger DNA sequencing. The dual luciferase reporter assay was used to detect the influence of two different haplotypes on GRIN1 gene expression.

RESULTS:

Seven SNPs (single nucleotide polymorphisms), including rs112421622 (- 2019 T/C), rs138961287 (- 1962--1961insT), rs117783907 (-1945G/T), rs181682830 (-1934G/A), rs7032504 (-1742C/T), rs144123109 (-1140G/A), and rs11146020 (-855G/C) were detected in the study population. Rs117783907 (-1945G/T) was associated with the occurrence of schizophrenia as a protective factor. The genotype frequencies of rs138961287 (- 1962--1961insT) and rs11146020 (-855G/C) were statistically different between cases and controls (p < 0.0083). The other four variations were not shown to be associated with the disease. Two haplotypes were composed of the seven SNPs, and distribution of T-del-G-G-C-G-G was significantly different between the case and control groups. However, the dual luciferase reporter assay showed that neither of the haplotypes affected luciferase expression in HEK-293 and SK-N-SH cell lines.

CONCLUSIONS:

The GRIN1 gene may be related to the occurrence of schizophrenia. Additional research will be needed to fully ascertain the role of GRIN1 in the etiology of schizophrenia.

• Authors: Yong-Ping Liu, Mei Ding, Xi-Cen Zhang, Yi Liu, Jin-Feng Xuan, Jia-Xin Xing, Xi Xia, Jun Yao, Bao-Jie Wang
• Journal: BMC medical genetics (BMC Med Genet) Vol. 20 Issue 1 Pg. 26 (01 31 2019) ISSN: 1471-2350 [Electronic] England
• PMID: 30704411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GRIN1 protein, human
• Nerve Tissue Proteins
• Receptors, N-Methyl-D-Aspartate

Topics

• Adult
• Asian People (ethnology, genetics)
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• HEK293 Cells
• Haplotypes
• Humans
• Male
• Middle Aged
• Nerve Tissue Proteins (genetics)
• Polymorphism, Single Nucleotide
• Receptors, N-Methyl-D-Aspartate (genetics)
• Regulatory Elements, Transcriptional
• Schizophrenia (ethnology, genetics)
• Sequence Analysis, DNA (methods)