Cloning and chromosome mapping of the human interleukin-1 receptor antagonist gene

Lennard, Andrew; Gorman, P.A.; Carrier, Martin; Griffiths, Samantha J.; Scotney, Hilary; Sheer, Denise; Solari, Roberto

doi:10.1016/1043-4666(92)90041-o

Cited by 54 publications

(25 citation statements)

References 22 publications

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“…IL-lra is encoded by the gene IL-IRN, which is located on the long arm of chromosome 2 in the cluster of IL-Io~, IL-I[3 and the two IL-l receptors (Lennard et al 1992;Nicklin et al 1994;Steinkasserer et al 1992). We have previously characterised a polymorphism that lies in intron 2 of the IL-1RN gene and that results from a variable number tandem repeat of an 86-bp sequence (Tarlow et al 1993a).…”

Section: Introductionmentioning

confidence: 97%

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus

et al. 1994

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Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1 alpha and IL-1 beta, and therefore is a powerful endogenous anti-inflammatory molecule. The gene encoding IL-1ra (designated IL-1RN) has a variable number tandem repeat polymorphism in intron 2. There are five alleles of the gene corresponding to 2, 3, 4, 5 and 6 repeats of an 86-bp sequence. We have determined allele frequencies in a control population and a group of 78 patients with lichen sclerosus. The frequency of one of the alleles is related to increasing disease severity. Thus, IL-1RN may be a candidate gene or severity factor for lichen sclerosus or may possibly be a linked marker to another, as yet undefined, gene.

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Section: Introductionmentioning

confidence: 97%

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus

et al. 1994

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“…The eDNA sequence of IL-lra derived from monocytes has been previously determined [3] and using an intronic polymorphism [4] the localization of the gone on chromosome 2 has been established by linkage analysis [5], as well as by in situ hybridisation [6].…”

Section: Introductionmentioning

confidence: 99%

Human interleukin‐1 receptor antagonist is expressed in liver

Steinkasserer

Estaller²,

Weiß³

et al. 1992

FEBS Letters

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“…Indeed, deletions in the region of exons 2-4 would not be selected against. Such deletions seem to have occurred over evolutionary time, since the region between the end of exon 1 and the start of exon 5 in human IL-lra (Lennard et al 1992) includes less than one-half as many base pairs as the region between exon 1 and exon 5 of human IL-113.…”

Section: I I Illmentioning

confidence: 99%

Evolution of the interleukin-1 gene family in mammals

Hughes

1994

J Mol Evol

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The phylogeny of interleukin-1 family genes shows that human interleukin-1 alpha (IL-1 alpha) is more closely related to IL-1 alpha of the bovine than to IL-1 alpha of the mouse, whereas human interleukin-1 beta (IL-1 beta) is more closely related to IL-1 beta of the mouse than to IL-1 beta of the bovine. The IL-1 receptor antagonist (IL-1ra) shows homology to the C-terminal region of both IL-1 alpha and IL-1 beta. In the C-terminal region, the IL-1 alpha genes of human and mouse have diverged more from each other at nonsynonymous sites than have either IL-1 beta or IL-1ra; because the same pattern is not seen at synonymous sites, it must be due not to a difference in mutation rate but rather to a greater degree of functional constraint on this region in the IL-1 beta and IL-1ra proteins than in the IL-1 alpha protein. But synonymous sites in IL-1 beta of mouse have evolved more rapidly than in IL-1 beta of human, indicating a higher rate of mutation in the former gene. In the N-terminal region of the protein, nonsynonymous sites have evolved at similar rates in IL-1 alpha and IL-1 beta. The first exon of the IL-1ra gene, which encodes the leader peptide, shows evidence of homology with the first exon of IL-1 beta, which is not translated. Thus, it seems likely that IL-1ra evolved by duplication of an IL-1 beta gene and loss of expression of exons 2-4.

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Cloning and chromosome mapping of the human interleukin-1 receptor antagonist gene

Cited by 54 publications

References 22 publications

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus

Human interleukin‐1 receptor antagonist is expressed in liver

Evolution of the interleukin-1 gene family in mammals

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