C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients
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Excessive activation of complement is associated with many diseases including schizophrenia. Investigation 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. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.
KeywordsC3 polymorphism Lipid metabolism Schizophrenia Acylation stimulating protein/C3adesArg
Body mass index
- HDL-C and LDL-C
High-density and low-density lipoprotein-cholesterol
This study was supported by a Grant from CIHR (to KC). K. Cianflone holds a Canada Research Chair in Adipose Tissue. C Bouchard is partially funded by the John W. Barton Jr Chair in Genetics and Nutrition. MHN was supported by an exchange scholarship from the Ministry of Higher Education and Scientific Research in Tunisia. We appreciate the technical and manuscript assistance of Mélanie Cianflone.
Conflict of interest
The authors declare that they have no conflict of interest.
- 11.Hernández-Mijares A, Jarabo-Bueno MM, López-Ruiz A, Solá-Izquierdo E, Morillas-Ariño C, Martínez-Triguero ML (2007) Levels of C3 in patients with severe, morbid and extreme obesity: its relationship to insulin resistance and different cardiovascular risk factors. Int J Obes 31:927–932CrossRefGoogle Scholar
- 12.Phillips CM, Goumidi L, Bertrais S, Ferguson JF, Field MR, Kelly ED, Peloso GM, Cupples LA, Shen J, Ordovas JM, McManus R, Hercberg S, Portugal H, Lairon D, Planells R, Roche HM (2009) Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome. Am J Clin Nutr 90:1665–1673CrossRefPubMedGoogle Scholar
- 16.Leban N, Haj Khelil A, Daimi H, Denden S, Slimene F, Mehdouani K, Abdennaji Guenounou B, Lefranc G, Perrin P, Ben Chibani J (2007) C3 complement polymorphism in patients suffering from obstructive chronic bronchopneumopathy in Tunisia. Ann Biol Clin (Paris) 65:251–256Google Scholar
- 18.Császár A, Duba J, Melegh B, Kramer J, Szalai C, Prohászka Z, Karádi I, Kovács M, Méhes K, Romics L, Füst G (2001) Increased frequency of the C3*F allele and the Leiden mutation of coagulation factor V in patients with severe coronary heart disease who survived myocardial infarction. Exp Clin Immunogenet 18:206–212CrossRefPubMedGoogle Scholar
- 26.Boyajyan A, Zakharyan R, Khoyetsyan A (2012) Molecular and genetic indicators of aberrant immunity and apoptosis in schizophrenia, Chapter XI. In: Sumiyoshi T (ed) Schizophrenia research: recent advances. Section II: neuropsychobiological insights, series: mental illnesses and treatments. Nova Science Publishers Inc, USA, pp 183–240Google Scholar
- 39.Heurich M, Martínez-Barricarte R, Francis NJ, Roberts DL, Rodríguez de Córdoba S, Morgan BP, Harris CL (2011) Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci USA 108:8761–8766CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Fisette A, Poursharifi P, Oikonomopoulou K, Munkonda MN, Lapointe M, Cianflone K (2013) Paradoxical glucose-sensitizing yet proinflammatory effects of acute ASP administration in mice. Mediat Inflamm 713284Google Scholar
- 42.Vancampfort D, Wampers M, Mitchell AJ, Correll CU, De Herdt A, Probst M, De Hert M (2013) A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls. World Psychiatry 12:240–250CrossRefPubMedPubMedCentralGoogle Scholar