Pro‐inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease

• Published in: International journal of rheumatic diseases Vol. 21; no. 5; pp. 1120 - 1126
• Main Authors: Assari, Raheleh, Aghighi, Yahya, Ziaee, Vahid, Sadr, Maryam, Rahmani, Farzaneh, Rezaei, Arezou, Sadr, Zeinab, Moradinejad, Mohammad Hassan, Raeeskarami, Seyed Reza, Rezaei, Nima
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2018
• Subjects: Alleles; Chi-Square Distribution; Child, Preschool; Children; Complications; cytokine; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotypes; Haplotypes; Humans; IL-1β; Infant; Inflammation; Interleukin-1alpha - genetics; Interleukin-1beta - genetics; Interleukin-6 - genetics; interleukin‐1; interleukin‐6; Iran; Kawasaki disease; Male; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - diagnosis; Mucocutaneous Lymph Node Syndrome - genetics; Mucocutaneous Lymph Node Syndrome - immunology; Odds Ratio; Phenotype; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Interleukin-1 - genetics; Retrospective Studies; Risk Factors; single nucleotide polymorphisms; Single-nucleotide polymorphism; Systemic vasculitis; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; cytokine; Kawasaki disease; interleukin-1; single nucleotide polymorphisms; interleukin-6
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.12911

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.