Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association Study of the ILAK1 Gene with Susceptibility to Systemic Lupus Erythematosus and Systemic Sclerosis.

Ota3,  Yuko, Kawaguchi1,  Yasushi, Kawamoto2,  Manabu, Takagi2,  Kae, Tochimoto2,  Akiko, Katsumata2,  Yasuhiro, Gono2,  Takahisa

Tokyo Women's Medical Univ, Tokyo, Japan
Tokyo Women's Medical Univ
Tokyo Women's Medical University, Tokyo, Japan
Tokyo Womens Med Univ, Shinjuku-ku, Tokyo, Japan

We explored whether single nucleotide polymorphisms (SNPs) in the Interleukin-1 receptor associated kinase-1(IRAK1) gene contribute to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) susceptibility in the Japanese population. Two hundred forty-four patients with SLE, 180 patients with SSc and 268 healthy controls (HC) were enrolled in this study. Four SNPs (rs2239673, rs763737, rs7061789, and rs5945174) in the IRAK1 gene were determined by allelic discrimination with the use of a specific TaqMan probe and PCR restriction fragment length polymorphism (PCR-RFLP). Association measured using either c2 or Fisher's exact test at the allelic and genotypic levels. Because IRAK1 is located on chromosome Xq28, cases and controls were stratified by gender and measured for each stratum.

In patients with SLE, the most common clinical manifestations in this study were nephritis (45%), cytopenia (32%), and neuropsychiatric manifestations (30%). The prevalence of butterfly rash was 17%, arthritis was 25%, serositis was 7%, and antiphospholipid antibody syndrome was 5%.

Both alleles and genotypes of all of the four SNPs in IRAK1 gene showed strong associations with SLE in female cohort (P < 0.0002; odds ratio = 1.9), although there were no associations between alleles and genotypes in the SNPs with whole SLE and in male cohort. In SLE, there were significant correlations between the allele of each SNP and nephritis. There were also significant differences in the frequencies of genotype of the SNPs between patients with butterfly rash or cytopenia and HC. In the frequency of genotype of rs5945174, there was a significant difference between patients with nephritis and HC. In patients with SSc, there were no association in the alleles and genotypes of the four SNPs in the ILAK1 gene.

In haplotype analyses, GGGG haplotype (defined as "G" at rs2239673, "G" at rs763737, "G" at rs5945174, "G" at rs7061789) was associated with susceptibility to Japanese patients with both SLE and SSc. The p value for association reached to 10-8and 10-2 respectively.In this study, we confirmed the association between an SNP in the IRAK1 gene and susceptibility to SLE in female Japanese population. Several autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, SLE and SSc are more common in women than men. Several mechanisms have been proposed as explanations for this gender bias. IRAK1, an X chromosome gene may have a critical role in the pathogenesis of SLE and SSc.

To cite this abstract, please use the following information:
Ota, Yuko, Kawaguchi, Yasushi, Kawamoto, Manabu, Takagi, Kae, Tochimoto, Akiko, Katsumata, Yasuhiro, et al; Association Study of the ILAK1 Gene with Susceptibility to Systemic Lupus Erythematosus and Systemic Sclerosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1587
DOI: 10.1002/art.29353

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