BACKGROUND: The relationship between cytokine gene polymorphisms and susceptibility to Kawasaki diseases (KD) is still controversial, so the aim of the present study was to investigate the association of 14 various polymorphisms of 9 cytokine genes (interleukin (IL)-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-A and transforming growth factor-B) with KD risk. METHODS AND RESULTS: A total of 211 KD children and 221 adult controls were recruited. All controls were frequency matched to KD patients on sex and ethnicity. PCR and TaqMan assays were used for genotyping. There were no significant differences between KD children and adult controls in the genotype or allelic type frequencies of the 14 polymorphisms. No significant associations were found between haplotypes, constructed by IL-1B, IL-4, IL-8, and IL-10 cytokine genes, and risk of KD. Additionally, a linear trend was observed when these single nucleotide polymorphisms were combined, as evidenced by an increasing risk of KD as the number of at-risk genotypes increased (P(linear trend)=0.002). In the stratification analysis of age and sex, there was a linear trend of KD risk as the number of at-risk genotypes increased among those aged >12 months (P=0.014) or female (P=0.001), respectively. CONCLUSIONS: No associations between individual cytokine genetic polymorphisms and susceptibility of KD were observed, but a gene-dosage effect on the risk of KD was found, especially for older or female subjects.
BACKGROUND: The relationship between cytokine gene polymorphisms and susceptibility to Kawasaki diseases (KD) is still controversial, so the aim of the present study was to investigate the association of 14 various polymorphisms of 9 cytokine genes (interleukin (IL)-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-A and transforming growth factor-B) with KD risk. METHODS AND RESULTS: A total of 211 KDchildren and 221 adult controls were recruited. All controls were frequency matched to KDpatients on sex and ethnicity. PCR and TaqMan assays were used for genotyping. There were no significant differences between KDchildren and adult controls in the genotype or allelic type frequencies of the 14 polymorphisms. No significant associations were found between haplotypes, constructed by IL-1B, IL-4, IL-8, and IL-10 cytokine genes, and risk of KD. Additionally, a linear trend was observed when these single nucleotide polymorphisms were combined, as evidenced by an increasing risk of KD as the number of at-risk genotypes increased (P(linear trend)=0.002). In the stratification analysis of age and sex, there was a linear trend of KD risk as the number of at-risk genotypes increased among those aged >12 months (P=0.014) or female (P=0.001), respectively. CONCLUSIONS: No associations between individual cytokine genetic polymorphisms and susceptibility of KD were observed, but a gene-dosage effect on the risk of KD was found, especially for older or female subjects.