title: Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia.
abstract: It has been established that cytokines play a critical role in the regulation of the CNS and recent studies have suggested that dysfunctions of both pro-inflammatory (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-1RA and IL-10) cytokines could be involved in the pathophysiology of schizophrenia. Previous studies have reported that functional polymorphisms in some cytokines genes may have important regulatory effects on such system. Therefore, the aim of the present study was to explore the possible role of the IL-1beta -511C/T and IL-1RA (86bp)(n) repeats polymorphisms in schizophrenia. A case control association study comparing genotype and allele frequencies in 346 northen Italian subjects (169 schizophrenic patients and 177 unrelated healthy volunteers) was performed. The frequencies of IL-1beta -511C and IL-1RA allele 1 (86bp)(4) are significantly higher in schizophrenic patients compared to controls (IL-1beta -511 P=0.047; IL-1RA (86bp)(n) P=0.002). Moreover our data show a protective effect of the IL-1RA allele 2 (86bp)(2) against schizophrenia (OR=0.59 95%CI:0.388-0.910; P=0.016) and this effect is enhanced by the concomitant presence of IL-1beta -511T (OR=0.48 95%CI:0.30-0.76; P=0.002). Our findings support the hypothesis that genetically determined changes in IL-1 metabolism regulation may contribute to the pathogenesis of schizophrenia confirming a role of IL-1 gene cluster in disease susceptibility.
authors.affiliation: Genetic Unit, I.R.C.C.S. San Giovanni di Dio- Fatebenefratelli, Via Pilastroni, 4, 25123, Brescia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Zanardini
authors.forename: Luisella
authors.initials: L
authors.lastname: Bocchio-Chiavetto
authors.forename: Catia
authors.initials: C
authors.lastname: Scassellati
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Gian Battista
authors.initials: GB
authors.lastname: Tura
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Jorge
authors.initials: J
authors.lastname: Perez
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D012795:Sialoglycoproteins / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha