Elsevier

Life Sciences

Volume 72, Issue 26, 16 May 2003, Pages 3017-3021
Life Sciences

Association study between interleukin-1β gene (IL-1β) and schizophrenia

https://doi.org/10.1016/S0024-3205(03)00248-0Get rights and content

Abstract

An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with the abnormal immune system, and cytokines may be important in schizophrenia. Among these cytokines, interleukin-1β may play a role in the pathogenesis of the disease. In the present study, we investigated the genetic association between a TaqI polymorphism in interleukin-1β gene (IL-1β) and schizophrenia by restriction fragment length polymorphism (RFLP) analysis among 132 Chinese families of Han descent. The transmission disequilibrium test (TDT) did not demonstrate an allelic association with schizophrenia. Our results suggested that the TaqI polymorphism in IL-1β gene might not confer increased susceptibility for schizophrenia.

Introduction

Schizophrenia is a severe psychiatric illness characterized by disturbance of thought, hallucinations and delusions. Family, twin and adoption studies strongly evidenced genetic susceptibility and a pattern of inheritance belonging to the class of multifactorial complex disorders [5]. Many hypotheses have been made to explain the pathophysiology of schizophrenia and accumulating evidence suggests that aberrant immune function may be implicated in the pathogenesis of this severe disease [1], [8].

Cytokines have been the recent focal points of immunological research in schizophrenia. They are expressed by neuronal and glial elements in the central nervous system and regulate normal and abnormal brain development [9], [10], [13]. Several lines of evidence indicate that proinflammatory cytokines may be important in schizophrenia [2]. In particular interleukin-1β (IL-1β) has been shown to modulate neuronal and glial cell growth during prenatal brain development in the human and rat's brain [14] and plays a key role as a differentiation factor promoting maturation of mesencephalic progenitor cells into dopaminergic neurons [11]. Therefore there is a need to determine whether IL-1β gene is associated with schizophrenia. Nucleotide search through the website (http://www.ncbi.nlm.nih.gov/) indicates that a TaqI polymorphism (rs 1143634) occurs in position 105 amino acid of IL-1β gene, which is a synonymous change (Phe 105 Phe). Although it is a “silent” site in which it has no effect on the gene product, this single nucleotide polymorphism (SNP) may still be informative, for example by being in linkage disequilibrium with a causal locus for schizophrenia. Therefore it is valuable to investigate the possibility that this polymorphism site at the IL-1β locus may be associated with schizophrenia.

Section snippets

Subjects

Schizophrenic patients and their biological parents were recruited for the present study at the Institute of Mental Health, Peking University, China. All the subjects were Chinese of Han descent. All patients met the ICD-10 criteria and underwent a structural clinical interview. Of the patients, 79 (59.8%) were male and 53 (40.2%) female, aged from 16 to 43. The mean duration of illness was 70 months. The clinical symptoms of patients were assessed by a trained psychiatrist using the Positive

Results

The genotype distributions and allelic frequencies were presented in Table 1.

Of the 132 families, 1 family had 2 heterozygous parents, and 19 families had 1 heterozygous parent. Among 264 parents, 21 were heterozygous, and transmitted 7 T and 14 C to their affected offspring with schizophrenia. The TDT was calculated using families with heterozygous parents. And the TDT analysis revealed that the differences in transmission were not statistically significant (XTDT2 = 2.333, P = 0.12) (Table 2).

Discuss

In this study, we found no association between the Taq I polymorphism in IL-1β gene and schizophrenia in Chinese people. This finding might suggest that the Taq I polymorphism in IL-1β gene do not play a major role in conferring susceptibility to schizophrenia. However, more than one data set indicate that serum IL-1β was significantly different between schizophrenic patients and controls [7], and IL-1β has been revealed to modulate the release of dopamine and norepinephrine in several brain

Acknowledgements

The work has been supported by grant H010210180112 from Beijing Biomedical R&D Innovation Program, grant 30000059 from the National Natural Scientific Foundation of China, grant 2000-A-A32 from Peking University Center for Human Disease Genomics, and grant 2002BA711A07 from National Key Project.

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