ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 972

Associations of Genetic Polymorphisms of Microrna-146a and Its Target Interleukin-1-Receptor-Associated Kinase 1 with Ankylosing Spondylitis

Chun-Huang Huang1, Jia-Yan Zhan2, Kai-Jieh Yeo3, James C. Wei4, Chih-Shien Chuang2 and Ruey-Hong Wong2, 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, 2Department of Public Health, Chung Shan Medical University, Taichung, Taiwan, 3Division of Allergy, Immunology and Rheumatology, Chung Shan Med Univ Hospital, Taichung, Taiwan, 4Allergy/Immunology/Rheumatolog, Chung Shan Med Univ Hospital, Taichung, Taiwan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Genetics and Genomics of Rheumatic Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose: Tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were important mediators of inflammation response in the development of ankylosing spondylitis (AS). Especially, microRNA (miR)-146a targets TNF-receptor-associated-factor-6 (TRAF-6) and interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress nuclear factor kB (NF-kB) activity and lipopolysaccharide (LPS)-induced inflammatory response. Here, we evaluated the effects of miR-146a rs2910164 G/C, IRAK1 rs3027898 A/C, and IRAK1 rs1059703 T/C genetic polymorphisms on the development of AS and clinical characteristics.

Methods: A total of 450 AS patients and 438 healthy controls were included, miR-146a genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism, and IRAK1 genetic polymorphisms were determined by the Taqman system.

Results: Our results showed that subjects possessing miR-146a rs2910164 GG genotype had 1.71-fold (95% confidence interval [C.I.] = 1.15-2.56) risk for AS development than those with GC/CC genotypes. Subjects with IRAK1 rs3027898 A allele (odds ratio [OR] = 1.54, 95% C.I. = 1.20-1.99) also had a significantly increased risk of AS than those with C allele. Further, subjects carrying both of miR-146a rs2910164 GG genotype and IRAK1 rs3027898 A allele had the highest risk (OR = 2.63, 95% C.I. = 1.25-5.55) for AS development than those with rs2910164 GC/CC genotypes and rs3027898 C allele, followed by subjects with rs2910164 GG genotype and rs3027898 C allele (OR = 1.75, 95% C.I. = 1.29-2.37) and subjects with rs2910164 GC/CC genotypes and rs3027898 A allele (OR = 1.57, 95% C.I. = 1.20-2.06). These results were also observed in males, but not in females. In addition, IRAK1 rs3027898 A/C and IRAK1 rs1059703 T/C polymorphisms were significantly associated with the abnormal erythrocyte sedimentation rate (ESR) level of AS patients, respectively. AS patients with both of miR-146a rs2910164 GG genotype and IRAK1 rs3027898 A allele had a 6.68-fold (95% C.I. = 2.83-15.73) risk for uveitis development than patients without.

Conclusion: MiR-146a rs2910164 G/C and IRAK1 rs3027898 A/C polymorphisms might be associated with the development of AS, as well as its clinical manifestations.

Disclosure:

C. H. Huang,
None;

J. Y. Zhan,
None;

K. J. Yeo,
None;

J. C. Wei,
None;

C. S. Chuang,
None;

R. H. Wong,
None.

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