Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.
Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. Electronic address: kapelski@wp.pl.
Pawel
P
Kapelski
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Maria
M
Skibinska
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research, Institute Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada.
Malgorzata
M
Maciukiewicz
Institute of Psychology, Kazimierz Wielki University, Bydgoszcz, Poland.
Monika
M
Wilkosc
Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.
Dorota
D
Frydecka
Department of Biochemistry, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poland.
Agata
A
Groszewska
Department of Pulmonology, Pediatric Allergy, and Clinical Immunology, Laboratory of Molecular and Cell Biology, Poznan University of Medical Sciences, Poznan, Poland.
Beata
B
Narozna
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Monika
M
Dmitrzak-Weglarz
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Piotr
P
Czerski
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Joanna
J
Pawlak
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Aleksandra
A
Rajewska-Rager
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Anna
A
Leszczynska-Rodziewicz
Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Agnieszka
A
Slopien
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Dorota
D
Zaremba
Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
Joanna
J
Twarowska-Hauser
D000328:Adult; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D044465:White People / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins; D018123:Receptors, Interleukin; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
Association; Functional polymorphism; Interleukin; Interleukin receptor