Drugs Targeting SNPrs35753505 of the NRG1 Gene May Prevent the Association of Neurological Disorder Schizophrenia in a Pakistani Population

Abstract

The Neuregulin 1 (NRG1) gene has been associated with schizophrenia in several populations, and all four types of NRG1 genes are linked with neurotransmitters activities. In this study for the first time we have demonstrated an association between NRG1 mutation and schizophrenia in Pakistani population. We examined the relationship of three genetic variants SNPs: rs3924999, rs2954041 and rs35753505 of NRG1 gene with the onset of disease. Genomic DNA samples were obtained from the blood of 100 patients and 80 matched controls. All three NRG1 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method and further confirmed by DNA sequencing. The SNPs frequencies were estimated by Hardy-Weinberg equilibrium and Chi-square tests. Our study established a significant association of rs35753505 with schizophrenia but no association with rs3924999 and rs2954041. The frequency of risk allele C was significantly higher (62.5%) in rs35753505 patients when compared to controls (28.13%). Genotype frequency by Hardy-Weinberg equilibrium for SNPrs3924999 in patients was GG 77.4%, GA 21.12% and AA 1.44% and showed no association with the disease. Similarly, no genotype association was observed in rs2954041: GG 92.98%, GT 6.89%, TT 0.13% of NRG1. However, one unexpected G allele, 100% guanine (G) with no adenine (A) was found to be present in SNP rs35753505 in both patients and controls. This is an interesting finding that both cohorts display only allele G peak but no peak for allele A in the electropherogram for this SNP. Our results suggest that SNP rs35753505 of NRG1 plays an important role in conferring susceptibility to the schizophrenia in a Pakistani population.

Genetic variation in NRG 1 gene and risk of post‐traumatic stress disorders in patients with hepatocellular carcinoma

“…rs35753505 of NRG1 plays an important role in conferring susceptibility to the schizophrenia in a Pakistani population . Besides, alleles at the rs3924999 of the NRG1 gene increase the risk of schizophrenia .…”

Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals

“…ErbB1 ligands, in particular, have been shown to negatively regulate GABAergic development in the neocortex and influence activity of glutamate receptor channels (Nagano et al 2007). In addition, genetic and candidate gene studies have implicated both ErbB1-4 and NRG1-6 in SZ (Barnes et al 2012; Deng et al 2013; Nawaz et al 2014). …”

Overview of schizophrenia research and treatment in Pakistan

“…However, published studies have demonstrated an association between NRG1 and TNF-α gene mutations and SCZ in the Pakistani population [81]. Earlier, Nawaz et al [14] and Naqvi et al [82] demonstrated that the NRG1 genetic variant SNP rs35753505 and polymorphism8nrg433E1006 plays an important role in conferring susceptibility to SCZ in the Pakistani population and may represent a potential antipsychotic drug target in such patients [15].Moreover, Amir et al provided strong evidence that supports the role of CACNA1C, GRM3, and DRD2 genes as schizophrenia susceptibility genes in the Pakistani population [74]. Nevertheless, one study has shown that some genetic variants rs1801028 and rs6277 of DRD2 are not associated with schizophrenia in the Pakistani population [83].…”

“…In addition to genetic makeup, various factors such as drug-addiction, underlie the predisposition toward SCZ. A large number of people in Pakistan, mostly men, are addicted to tobacco, cannabis, betel nut, charas, and other illicit drugs [14]. Repeated administration of these stimulants at a younger age (<15 years) increases the likelihood of developing SCZ [15].…”