Possible association between Interleukin-1beta gene and schizophrenia in a Japanese population

Abstract

BackgroundSeveral lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1β) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms.MethodsA total of 533 patients with schizophrenia (302 males: mean age ± standard deviation 43.4 ± 13.0 years; 233 females; mean age 44.8 ± 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 ± 17.3 years; 748 females; 46.3 ± 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia.ResultsSignificant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032).ConclusionsThe present study shows the first evidence that the IL-1β gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1β gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1β in the etiology of schizophrenia.

Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers

“…Introns can contribute to the enhancement of translation of gene products, possibly due to mechanisms including transcription initiation, termination, and regulation (Shabalina et al, 2010). A prior report found that this IL1B polymorphism was associated with cortisol response to dexamethasone challenge in a sample of 179 adults (Sasayama, Hori, Iijima, et al, 2011). Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis is well established in association with early stress exposure and internalizing symptoms and disorders (Carpenter et al, 2007; Carpenter, Shattuck, Tyrka, Geracioti, & Price, 2011; Hartman, Hermanns, de Jong, & Ormel, 2013; Lupien et al, 2009; Morris, Compas, & Garber, 2012; Stetler & Miller, 2011).…”

“…The IL1B G +5810 A (rs1143633) single nucleotide polymorphism (SNP) was genotyped by the TaqMan method using an ABI PRISM 7900 Sequence Detection System (ABI, Foster City, CA, USA). This SNP was selected because it has previously been associated with inflammatory phenotypes (Hahn, Cho, Kim, Kim, & Kang, 2009; Moxley, Han, Stern, & Riley, 2007; Solovieva et al, 2009), cognitive function (Sasayama, Hori, Teraishi, Hattori, Ota, Matsuo, et al, 2011), schizophrenia (Sasayama, Hori, Teraishi, Hattori, Ota, Iijima, et al, 2011), and with cortisol response to dexamethasone administration (Sasayama, Hori, Iijima, et al, 2011). …”

The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review

“…Crucial to the IL-1 receptor signaling pathway [40,49,50]. SRY Y May be involved in dopamine regulation [53].…”

“…Additionally, MECP2 has recently been shown in animal models to be an integral component for GABA release from neurons [45]. Of note, GABAergic dysfunction has been long thought to be involved in the pathogenesis of schizophrenia [46,47] [40,49,50]. IL-1β is also hypothesized to participate in immunological reactions involving infections in utero, which may then lead to deleterious effects on a developing neurological system [40,51].…”

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

“…Furthermore, some studies reported significant associations of IL-1β polymorphisms with schizophrenia (Hanninen et al , 2008, Papiol et al , 2004, Sasayama et al , 2011a, Zanardini et al , 2003 and with depression (Borkowska et al ,…”