ORIGINAL PAPER C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients Mohamed Jalloul Nsaiba • Marc Lapointe • Hajer Mabrouk • Wahiba Douki • Lotfi Gaha • Louis Pe ´russe • Claude Bouchard • Besma Bel Hadj Jrad • Katherine Cianflone Received: 2 May 2014 / Revised: 13 January 2015 / Accepted: 16 February 2015 Ó Springer Science+Business Media New York 2015 Abstract Excessive activation of complement is associ- ated with many diseases including schizophrenia. Investi- gation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross- sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p \ 0.05–0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p \ 0.05–0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Fur- ther, proportional conversion of C3 to ASP (%ASP/C3) also increased (p \ 0.0001, GG [ CG [ CC). C3 polymor- phisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permis- sive for complement pathway activation and dyslipidemic influences. Keywords C3 polymorphism Á Lipid metabolism Á Schizophrenia Á Acylation stimulating protein/C3adesArg Abbreviations BMI Body mass index C3 Complement 3 HDL-C and LDL-C High-density and low-density lipoprotein-cholesterol TG Triglyceride SZ Schizophrenic NOR Normal Introduction The complement system, a major effector of specific humoral response plays a crucial role in innate immunity and also regulates the adaptive immune processes [1]. Complement activation is fundamental to the immune defense of the host, but if it becomes excessive, uncon- trolled or poorly targeted, it can lead to various diseases including inflammatory and cardiovascular diseases. M. J. Nsaiba Á M. Lapointe Á K. Cianflone (&) Centre de Recherche de l’Institut Universitaire de Cardiologie & Pneumologie de Que ´bec, Universite ´ Laval, Y4332, 2725 Chemin Ste-Foy, Que ´bec, QC G1V 4G5, Canada e-mail: katherine.cianflone@criucpq.ulaval.ca M. J. Nsaiba Á B. B. H. Jrad Laboratoire Ge ´ne ´tique, Biodiversite ´ et Valorisation des Bio- ressources (LR11ES41), Institut Supe ´rieur de Biotechnologie de Monastir, Monastir, Tunisie H. Mabrouk Á W. Douki Á L. Gaha Research Laboratory Vulnerability to Psychotic Disorders, LR05ES10, Psychiatry Department, University Hospital of Monastir, Monastir, Tunisie L. Pe ´russe Department of Kinesiology, Faculty of Medicine, Institute of Nutrition and Functional Foods, Universite ´ Laval, Que ´bec, QC, Canada C. Bouchard Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA 123 Neurochem Res DOI 10.1007/s11064-015-1543-z