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A7.13 IRAK1 Rs3027898 Polymorphism: A Variant Implicated in the Pathogenesis of more than one Inflammatory Disease
  1. A Chatzikyriakidou,
  2. PV Voulgari,
  3. AA Drosos
  1. Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Greece

Abstract

Background and Objectives IRAK1 plays significant role in TLR dependent activation of the transcription factor NF-kB, which subsequently increases the expression of many genes such as TNF-α and IL-8 related to immunological reactions. Polymorphism Rs3027898 located in the 3′-untranslated region of IRAK1 gene was studied for its association with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) predisposition.

Materials and Methods The polymerase chain reaction-single strand conformation polymorphism analysis coupled with sequencing was used as the screening method for variant genotyping in 136 RA, 29 PsA, and 49 AS patients and 147 controls.

Results IRAK1 polymorphism Rs3027898 was revealed to be associated with all the studied inflammatory conditions. Specifically, strong statistically significant difference was observed in polymorphism distribution between RA patients and controls (p = 0.044), PsA patients and controls (p < 0.001), and AS patients and controls (p < 0.001). Grouping genotypes AA and AC versus CC the statistical difference was also significant in all groups: RA versus controls (p = 0.017), PsA versus controls (p < 0.001), and AS versus controls (p = 0.010).

Conclusions Here, we report IRAK1 gene polymorphism association with RA, PsA, and AS. This variant, previously, was also related to RA in patients with Chinese origin, with atherothrombotic cerebral infarction in Japanese patients, while we also revealed its association with ischemic stroke. In addition, another IRAK1 gene polymorphism (Rs1059703) was also related to atherothrombotic cerebral infraction, high CRP, chronic kidney disease, the induction of vaccine-induced immunity and sepsis outcomes but this variant did not differ significantly between our studied groups and controls (data not given). Taking into account that IRAK1 gene affects the activation of transcription factor NF-kB, which is implicated in many immune related genes’ expression, we could understand IRAK1 extensive association with many inflammatory conditions beyond patients’ origin.

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