Specific Mutations In The IL2RA Gene Associated With Juvenile Idiopathic Arthritis

Main Category: Arthritis / Rheumatology
Also Included In: Pediatrics / Children's Health;  Genetics;  Clinical Trials / Drug Trials
Article Date: 16 Jun 2008 - 0:00 PST

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Certain single nucleotide polymorphisms (SNPs) within the interleukin 2 receptor alpha (IL2RA) gene region are shown to be associated with juvenile idiopathic arthritis (JIA), according to a new study of two independent cohorts presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

In the study, three specific SNPs (small variations in the genetic code), rs2104286, rs41295061 and rs11594656, were investigated as previous studies reported an association of these with rheumatoid arthritis, multiple sclerosis and type 1 diabetes.

The researchers found that one of the SNPs, (rs2104286), was significantly associated with UK cases of JIA (allelic odds ratio = 0.76 95% confidence interval 0.66-0.88, trend p=0.0002), and the association was strongest in a cohort of patients with oligoarthritis, the most common subtype of JIA. This SNP was most strongly associated with female patients and those positive for antinuclear antibodies (see Editors Note). A second SNP (rs41295061), one of two SNPs previously associated with type 1 diabetes, also showed modest evidence for association with JIA (odds ratio 0.80 95% confidence interval 0.63-1.0, trend p=0.05).

In the study, the three SNPs (rs2104286, rs41295061 and rs11594656) were selected for genotyping in UK JIA cases (n=654) and controls (n=3849). Genotype data for SNP rs2104286 for controls was combined with the data for that SNP obtained from a genome-wide association study (WTCCC GWA), giving a total control sample size of 6787. Genotyping was performed using the SEQUENOM iPlex platform. Association analysis was performed using PLINK, a genome data analysis toolset. Stratification into groups in line with the commonly accepted seven categories of JIA (called ILAR subgroups), ANA antibody status and gender was performed. Data for rs2104286 was also available, from a GWA studies of Caucasian North American JIA cases (n=747) and controls (n=1161).

This association with rs2104286 was replicated in a second study cohort of JIA cases from the USA (odds ratio 0.84 95% confidence interval 0.65-1.0, trend p=0.05). There was no significant evidence for heterogeneity between the UK and North American datasets, and meta-analysis of the two cohorts yielded highly significant evidence for association (odds ratio 0.76 95% confidence interval 0.62-0.88, p-value 4.9 x 10-6).

Dr Wendy Thomson of the University of Manchester, UK who led the study, said: "The IL2RA gene has previously been shown to be associated with type 1 diabetes, Graves' disease, rheumatoid arthritis and multiple sclerosis, and so may be linked with a predisposition to autoimmunity in general. Our results have shown that the genetic variants of the IL2RA gene are strongly associated with JIA in two independent cohorts. Further investigation of this gene will aid our understanding of the pathogenesis of these diseases, and hopefully lead to future treatment approaches."

As many as one in 1,000 children has arthritis, most commonly in the form of JIA. The condition causes pain, stiffness and joint swelling, which can impact fine motor skills (e.g. writing), concentration, mood and sleep.

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Article adapted by Medical News Today from original press release.
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The three main types of JIA are:

• Oligoarticular/pauciarticular (accounting for approximately 50% of cases, it affects up to four joints at presentation, usually in the lower limbs)
  
  
• Polyarticular (accounting for approximately 20% of cases, it affects more than five joints)
  
  
• Systemic (accounting for approximately 10% of cases, it affects all joints)

Antinuclear antibodies (ANAs) are unusual antibodies, that are specifically capable of binding to certain structures within the cell nucleus. ANAs are more commonly found in patients whose immune system 'attacks' its own tissues, i.e. those suffering from rheumatic diseases.

Abstract number: OP0201

About EULAR

• The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.
  
  
• The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.
  
  
• Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

Source: Rory Berrie
European League Against Rheumatism