Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

Abstract

Background/Aims: Several lines of evidence point to the role of neurobiological mechanisms and genetic background in bipolar disorder (BD). The interleukin-1 receptor antagonist (IL-1Ra) is the principal regulator of IL-1α and IL-1β bioactivities. This study aimed to investigate the potential role of the variable number of tandem repeats (VNTR) polymorphisms of the IL-1Ra gene (IL1RN) in conferring susceptibility to BD. Methods: In total, 217 patients meeting DSM-IV-TR criteria for BD and 212 controls were recruited for the study. Genotyping of IL1RN was determined by polymerase chain reaction amplification of VNTR of 86 base pairs in intron 2 of IL1RN. Results: The genotype distribution of IL1RN polymorphism was significantly different between BD patients and controls. The IL1RN*1/2 genotype was more prevalent in BD patients than in controls (44.2 vs. 30.2%, p = 0.003). Multiple logistic regression analysis demonstrated that IL1RN*1/2 heterozygotes had a significantly higher risk for BD (OR 1.83 and 95% CI 1.22–2.74, p = 0.003). Further stratification of the BD patients into IL1RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1RN*2 carriage and prolongation of the disease (p = 0.02). Conclusions: These findings suggest a positive association between VNTR polymorphism in IL1RN and BD. Additional studies, particularly with a prospective approach, are necessary to clarify the precise role of the VNTR polymorphism on the disease in different ethnic populations.

Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro

“…8). All these validated genes have been suggested to play important roles in the CNS and neurological disorders [23, 48–53]. Our validation by PCR confirmed that the Meth treatment has the capacity to directly stimulate the upregulation of these genes, which have an involvement in inflammatory processes in the brain.…”

Infectious and immunogenetic factors in bipolar disorder

“…In the same locus, another study in the Iranian population on the À511 C>T (rs16944) polymorphism found that the T allele carrier state is associated with BD (71), an allele previously linked with longer episodes and total brain and more specifically left dorsolateral prefrontal cortex grey matter deficits when compared to the non-T allele carrier counterparts (71,77). Although two other studies regarding the same VNTR (variable number tandem repeat) of 86 bp in length in intron 2 of the IL1RN gene (interleukin-1 receptor antagonist) did not confirm this association in the Korean and Iranian populations, Rafiei et al, in a Iranian sample, after having stratified BD patients into two subgroups according to age at onset, found that presence of the allele containing two repeats was associated with later onset (71,76,78,79). This allele is associated with more prolonged and severe proinflammatory immune responses (80).…”

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