Gene Therapy and Molecular Biology Vol 13, page 152 152 Gene Ther Mol Biol Vol 13, 152-157, 2009 Association analysis of the Tumor necrosis factor gene polymorphisms (TNFA 238 and 302) in the development of schizophrenia: Impact on the antipsychotic treatment response Research Article Chi-Un Pae 1,2* , Antonio Drago 3 , Alberto Chiesa 3 , Laura Mandelli 3 , Alessandro Serretti 3 , Tae-Youn Jun 1 1 Department of Psychiatry, The Catholic University of Korea College of Medicine, Bucheon, Kyounggi-Do, Republic of Korea 2 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA 3 Institute of Psychiatry, University of Bologna, Bologna, Italy __________________________________________________________________________________________________ *Correspondence: Chi-Un Pae, MD, PhD, Department of Psychiatry, Holy Family Hospital, The Catholic University of Korea College of Medicine, 2 Sosa-Dong, Wonmi-Gu, Bucheon, Kyeonggi-Do 420-717, Republic of Korea; E-mail: pae@catholic.ac.kr Key Words: schizophrenia, tumor necrosis factor-α gene, and clinical variables. Received: 25 May 2009; Revised: 2 June 2009; Accepted: 4 June 2009; electronically published: 5 June 2009 Summary This study investigated the tumor necrosis factor-α gene (TNFA; -238 G/A and -308 G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the two polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) were used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with TNFA -238 A allele (genotype AA plus AG) and presence of family history was found (p=0.023). No significant interaction effects between TNFA –238 and -308 polymorphisms either on the development of schizophrenia or on clinical variables such as antipsychotics treatment response and psychopathology were found, although a significant interaction effect for subjects carrying TNFA -238 AG and -308 AA genotypes on a positive family history was observed (p=0.017). These results suggest that the interaction effects between TNFA –238 and -308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in Korean population. I. Introduction Various cytokines have been known to form the network between the immune system and the central nervous system. These cytokines show a change not only in the peripheral immune system but also in the central nervous system, and they exert their effects on the proliferation and death of immune cells; they are associated with neurotransmitters metabolism, neuronal development and degeneration (Muller and Ackenheil, 1998). TNF-α is a very important pro-inflammatory cytokine involved in the regulation of immune system and in the initial stage of inflammatory reaction, and it has been related to abnormal behaviors, anxiety, decreased appetite, emotions, sleep disturbances, recognition and other psychiatric symptoms highly expressed also in schizophrenia (Holden and Pakula, 1999;Kubota et al., 2001;Reichenberg et al., 2001;Strieter et al., 1993). In addition, the serum concentration of TNF-α in schizophrenic patients has been reported to be elevated in comparison with the control group. Moreover, after the administration of antipsychotic drugs, an alteration of its concentration has been detected, and thus its involvement not only in the development of schizophrenia but also in the response to treatment has been suggested (Erbagci et