Pro-Inflammatory Cytokine Single Nucleotide Polymorphisms in Kawasaki Disease Publisher Pubmed



Assari R^{1, 2} ; Aghighi Y³ ; Ziaee V^{1, 2} ; Sadr M⁴ ; Rahmani F⁵ ; Rezaei A⁵ ; Sadr Z⁴ ; Moradinejad MH² ; Raeeskarami SR⁶ ; Rezaei N^{5, 7, 8} Show Affiliations
Source: International Journal of Rheumatic Diseases Published:2018

Abstract

Aim: Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. Methods: Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at −889 (rs1800587), IL-1β at −511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at −308 (rs1800629), TNF-α at -238, IL-6 at −174 (rs1800795) and IL-6 at +565. Results: Twenty-one percent of the control group had A allele at TNF-α −238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14–0.71]). Consistently, TNF-α genotype GG at −238 had significant association with KD (OR [95% CI] = 4.31 [1.79–10.73]). Most controls carried the CG genotype at IL-6 −174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (−308, −238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. Conclusion: TNF-α GG genotype at −238 and GG haplotype at positions −308 and −238 were associated with KD in an Iranian population. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd