Potential role of Neuregulin 1 and TNF-alpha (2308) polymorphism in schizophrenia patients visiting hospitals in Lahore, Pakistan Mamoona Naz • Maria Riaz • Mahjabeen Saleem Received: 4 March 2010 / Accepted: 24 November 2010 / Published online: 3 December 2010 Ó Springer Science+Business Media B.V. 2010 Abstract Schizophrenia is a chronic and disabling dis- ease of the brain. Schizophrenic patients have auditory hallucinations, delusions and reduced social skills. Recent studies suggest that the genetic polymorphisms are linked with development of schizophrenia. Polymorphisms of schizophrenia susceptibility and different cytokine genes act as the genetic markers. The objective of our study is to examine the association between the neuregulin 1 and tumor necrosis factor-a (-308) gene polymorphism with schizophrenia. This association was performed on the basis of molecular biology to screen the mutations of neuregulin 1 and tumor necrosis factor-a (-308) gene in schizo- phrenic patients by polymorphism analysis. Statistical analysis of the observed data shows that there was an association (P = 0.003) between patient’s group and con- trols in terms of genotypes of single-nucleotide polymor- phism 1 rather than single-nucleotide polymorphism 2 of neuregulin 1. So, heterozygous (adenine/guanine) allelic pattern can be a higher risk factor of schizophrenic patients. Polymorphism of tumor necrosis factor-a (-308) gene indicated frequent presence of homozygous (adenine/ adenine) allelic pattern in patient’s group than in controls (P = 0.015). Statistical analysis indicates that the age distribution has significant difference between patient’s group and controls (P = 0.022) while the gender ratio is not significantly different (P = 0.366) between the two groups. It was concluded that in Pakistani population the neuregulin 1 and tumor necrosis factor-a (-308) genes are strongly associated with schizophrenia. Keywords NRG 1 Á TNF-a Á Schizophrenia Introduction Schizophrenia is a serious mental illness. It is characterized by disturbances in thought process, abnormalities in the expression of reality and behavior of the person [1]. Schizophrenic patients have social difficulties, history of behavioral irregulation and primarily learning. Disturbed thought processes, delusions, auditory hallucinations and reduced social skills are some of the diagnostic features of schizophrenia [2]. The abnormal functioning of the immune system including the irregulation and malfunction of different parameters of immune system are strongly associated with pathogenesis of schizophrenia. There is a strong relationship between the clinical characteristics of schizophrenia and disturbances of the immune system [3]. Cytokines are biological factors that are involved in several immunological functions in different physiologic and pathologic conditions and also play a central role as mediators between the central nervous system (CNS) and the immune system [4, 5]. Tumor necrosis factor (TNF) is involved in proinflam- matory, catabolic and immunoregulatory actions and hence plays a central role in the etiopathogenesis of schizophrenia because of its cytotoxic role in different neurologic disor- ders. Abnormal level of TNF-a may effect proper func- tioning of the brain [6, 7]. The TNF-a gene is located on the short arm of chro- mosome 6 (6p21.1–21.3) which is a locus linked with the genetic susceptibility of schizophrenia [8, 9]. Several studies demonstrated that the TNF-a gene may be consid- ered as a functional candidate gene for schizophrenia, the promoter region of this gene is also involved in functional M. Naz Á M. Riaz Á M. Saleem (&) Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore 54590, Pakistan e-mail: mahjabeensaleem1@hotmail.com 123 Mol Biol Rep (2011) 38:4709–4714 DOI 10.1007/s11033-010-0606-0