Background The pathogenesis of ankylosing spondylitis (AS) has strongly been associated with the gene HLA-B27; however, AS occur only in 1%–5% of HLA-B27-positive individuals and increasing evidence suggests involvement of also non-HLA genes. Previous work has confirmed association with single nucleotide polymorphisms in interleukin-23 receptor (IL-23R).
Objectives The aim of the study is to confirm the association of IL-23R gene polymorphisms with ankylosing spondylitis in Turkish population and to find out possible mutations responsible from this association.
Methods We included 48 AS patients and 48 healthy unrelated individuals. Extracted DNA from patient specimens was amplified with polymerase chain reaction and sequenced.
Results We identified 6 new point mutations at IL-23R gene in patients with AS (Table). 2824DelC mutation (1/41 - 2,4%) was found to be in the intronic region that probably does not have an effect on the protein. 34521GT mutation (1/36 - 3,8%) was located at the exon-intron boundary and changes the exon recognition site. This should be the reason for exon skipping. The mutation probably changes the protein structure and function of IL-23R protein. Ala228Ala (2/42 - 4,8% - p.0,0306) was a silent mutation that does not change the protein structure of the IL23R protein. Ala364Gly mutation (6/43–17% - p.0,074) missense mutation was found at 6 patients as a heterozygote. Ala364Gly mutation looks associated with AS. Leu371Phe mutation (1/43 - 2,3%) was also missense mutation and caused change on the aminoacid. As the last point, Tyr436Stop is a silent mutation that is an early stop truncating the protein 194 aminoacid earlier than the usual process.
Conclusions We have determined 6 new point mutations in 11 patients included. Although two of the mutations probably do not have an effect on the protein, other four mutations cause changes in the protein structure of IL-23R protein. We consider that these mutations probably contribute to the pathogenesis of AS by effecting the functions of the protein.
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Karaderi T, Harvey D, Farrar C, et al. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series. Rheumatology (Oxford). 2009 Apr;48(4):386–9.
Disclosure of Interest None declared