title: 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.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Nawaz
authors.forename: Huma
authors.initials: H
authors.lastname: Asif
authors.forename: Asifullah
authors.initials: A
authors.lastname: Khan
authors.forename: Hina
authors.initials: H
authors.lastname: Ishtiaq
authors.forename: Fatima
authors.initials: F
authors.lastname: Shad
authors.affiliation: Department of Neuroscience, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. siddisbs@yahoo.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Siddiqui
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1