Polymorphisms of IRAK1 Gene on X Chromosome Is Associated with Hashimoto Thyroiditis in Korean Children

Abstract

Autoimmune thyroid disease (AITD) is predominant in females and has been focused on the sexual diploid in immune response. The IL-1 receptor-associated kinase 1 (IRAK1) gene on the X chromosome was recently suggested as strong autoimmune disease-susceptible loci, second to the major histocompatibility complex region. We investigated the frequency of IRAK1 single-nucleotide polymorphisms (SNPs) in children with AITD. In this study, we observed that SNPs of IRAK1 including rs3027898, rs1059703, and rs1059702 in 115 Korean AITD pediatric patients (Graves' disease = 74 [females = 52/males = 22]; Hashimoto disease [HD] = 41 [females = 38/males = 3]; thyroid-associated ophthalmopathy [TAO] = 40 (females = 27/males = 13); without TAO = 75 (females = 63/males = 12); total males = 25, total females = 90; mean age = 11.9 years) and 204 healthy Korean individuals (males = 104/females = 100). The data from cases and controls were analyzed from separate sex-stratified or all combined by χ 2 test for categorical variables and Student t test for numerical variables. Our study revealed that SNPs of IRAK1-associated HD and without TAO but Graves' disease and TAO were not found significant. When cases and controls were analyzed by separate sex, we found that rs3027898 AA, rs1059703 AA, and rs1059702 GG showed disease susceptibility in female AITD, HD, and without TAO. Also, all rs3027898, rs1059703, and rs1059702 were found to be in strong linkage disequilibrium (D' = 0.96-0.98, r2 = 0.83-0.97). The haplotype of 3 SNPs was higher in AITD than in controls (CGA, r2 = 5.42, P = 0.019). Our results suggest that IRAK1 polymorphisms may contribute to the pathogenesis of HD, AITD, and without thyroid-associated ophthalmopathy for females.

Keywords: Graves’ disease; Hashimoto’s thyroiditis; IRAK1 polymorphism; X chromosome genetic analysis; autoimmune thyroid disease; thyroid-associated ophthalmopathy.