Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Interleukin 1 (IL1) (IL1A and IL1B) genes polymorphisms 

IL1A (interleukin 1 alpha) and IL1B (interleukin 1 beta) genes, located in the long arm of chromosome 2 (2q14.1) encode, respectively, the proteins interleukin-1α (IL-1α) and interleukin-1β (IL-1β). These interleukins are cytokines, which are involved in cell-to-cell communication and have a wide variety of functions within the immune system. In general, all interleukins are produced by tissue macrophages, blood monocytes, fibroblasts, ..., when activated. There is a group of them that are called pro-inflammatory because they stimulates the activity of genes involved in inflammation and immunity (IL1, IL-6, TNF-α, IFN-γ), being produced by cells that exercise the function of natural immunity (monocytes and macrophages) and by Th1 cells. There are other interleukins that are considered anti-inflammatory (IL-4, IL-5, IL-10, IL-13 ...), because they exert an opposite action and are synthesized by Th2 cells.

Interleukin-1 (IL-1), released by phagocytic cells, exerts its action on T cells, inducing in them the release of IL-2 that stimulates the maturation and proliferation of B cells, in addition to other functions on other cells. By stimulating inflation as a natural defense mechanism, it plays a critical role in protecting our body from foreign invaders such as bacteria or viruses. In addition, it is involved in the febrile response and is known as an endogenous pyrogen for inducing fever after release. It also stimulates the release of prostaglandins, and participates in bone resorption, excising and removing unnecessary bone tissue.

Interleukin-1α is initially produced as a relatively long protein that is trapped within cells. Another protein, called calpain, cleaves this precursor protein to create a shorter, mature version of interleukin-1α. The shorter form of this protein is secreted by immune system cells to influence the functions of other cells. Interleukin-1β (IL-1β), also synthesized as a proprotein, would be activated by a "caspase."

IL-1α and IL-1β contain 271 and 269 amino acids, respectively, and have only 26% homology to each other at the amino acid level in their respective proteins, and 45% homology at the nucleic acid level of the gene that encodes them.

Variations (polymorphisms) in the IL1A gene have been studied as potential risk factors for several other disorders associated with abnormal inflammation. For this reason, they have been found involved in cardiovascular disease, periodontal disease, idiopathic inflammatory myopathy, chronic osteomyelitis, intervertebral disc disease, ankylosing spondylitis (AS), some varieties of glaucoma (keratoconus), rheumatoid arthritis, systemic-onset juvenile idiopathic arthritis (Still’s disease), crystal-induced arthropathy, systemic lupus erythematosus (SLE), and even in some forms of kidney disease, neurodegenerative diseases, Alzheimer's disease, or gastric cancer related to Helicobacter pylori infection.

The most well-studied variation (polymorphisms) affecting the IL1A gene is a change in a single nucleotide in a 5´-UTR region of regulatory DNA (IL1A -889 C>T; rs1800587) which changes a single nucleotide in the gene (C;T heterozygous or T;T homozygous). This variation affects the production of interleukin-1α within cells. Research has also identified a second common variation in the exon 5 of the IL1A gene (IL1A +4845 G>T, rs17561) which changes a single nucleotide in the gene (G;T heterozygous or T:T homozygous). This variation likely affects the sensitivity of interleukin-1α to cleavage by calpain. In the exón 5 of the ILB gene, the IL1B +3954 (C>T) polymorphism (rs1143634, C;T heterozygous or T:T  homozygous) has been found. Others polymorphism have also been described in the IL1A gene (rs1304037 +10897; rs2071375; rs2071376 +6637; rs2071375 +5418; rs2071373 +1986; rs1894399 +1893), IL1B gene (rs16944 -511; rs1143627 -31) or IL1RN gene (IL1 receptor: rs419598 +2018).

The relation between the polymorphisms of the IL1A and IL1B genes and the intensity of periodontitis in non-smoking adults was suggested in 1977. It is currently recognized that there is a relation between some forms of periodontitis and the IL1A-889 polymorphisms, and IL1B + 3953. In this sense, it was found that, in non-smoking individuals aged 40 to 60, with the "2" allele, both in a homozygous and heterozygous state, there were 19 times more risk of developing severe periodontitis compared to the homozygous allele "1". Subsequently, many studies have been carried out that correlate the development of early onset periodontitis (EOP: Early Onset Periodontitis), in its juvenile clinical forms (localized or generalized).

          Currently, the following facts are admitted in the relation of periodontitis and polymorphisms of the IL1 gene: a) IL1 polymorphisms would not have a high relationship with the development of aggressive periodontitis; b) IL1 polymorphisms would imply a greater predisposition to develop chronic periodontitis; c) The IL1 polymorphism would be a useful marker, only in those populations in which that polymorphism had little distribution, but not in those populations in which the polymorphism was widely distributed; d) The risk of periodontitis due to ILA polymorphism is independent of smoking; e) The polymorphism of the IL1 gene would be one of several genetic factors in the development of chronic periodontitis.

Tests performed in IVAMI: in IVAMI we perform the detection of polymorphisms of interleukin-1α (IL1A) (polymorphism ILIA-889, rs1800587 in the 5´-UTR región and IL1A+4845, rs17561 in the exon 5) and interleukin-1β (IL1B) (polymorphism IL1B+3954, rs1143634 in the exon 5) genes, by means of the complete PCR amplification of the exons of both genes, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).