Association of interferon regulatory factor 5 (IRF5) markers with an increased risk of lupus and overlapping autoimmunity in a Kuwaiti population.

BACKGROUND

Variations in IRF5 have been associated with an increased risk of developing lupus (SLE).

AIM

To explore the association of IRF5 markers (rs2004640, rs10954213) with susceptibility to SLE and to the development of more than one autoimmune disease (OP) and to analyse the influence of rs2004640 on IRF5 isoform expression.

METHODS

A total of 300 age/gender/ethnicity-matched Kuwaitis were screened using the TaqMan®SNP Genotyping Assay. Data analysis was conducted in three groups: patients with high/low anti-dsDNA antibody titre, lupus nephritis/non-nephritis and disease onset age ≤28 years/>28 years. cDNA samples with defined rs2004640 genotypes were amplified using specific primers and transcripts associated with each of the exon1 variants were detected on polyacrylamide-gel.

RESULTS

A significant association was observed between the IRF5 markers (rs2004640, rs10954213) and susceptibility to SLE (p < 0.0001) and OP (p < 0.025). Stratified analysis showed a significant association of the rs2004640 T-allele with a high titre of anti-dsDNA antibody (p = 0.0035, OR = 1.92) and a low disease onset age ≤28 years (p = 0.0026, OR = 1.94). Additionally, the influential role of the rs2004640 T allele on IRF5 expression was observed.

CONCLUSIONS

This study is the first to investigate the association of IRF5 markers with OP and the very first to explore the association of these markers with SLE in Arabs. The novelty of this study is the association of the rs2004640 T-allele with increased anti-dsDNA antibody production and SLE in a younger age group.