ABSTRACT
Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (-1082, -819, and -592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci -819 T > C and -592 A > C for KD cases was observed (P permutation = 0.029 and P permutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090-2.443; P permutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. The haplotype CC (-819, -592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987-1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and -592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.
Subject(s)
Genetic Association Studies , Interleukin-10/genetics , Mucocutaneous Lymph Node Syndrome/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Case-Control Studies , Child, Preschool , Female , Haplotypes , Heredity , Humans , Infant , Male , TaiwanABSTRACT
BACKGROUND: The literature regarding interleukin (IL)-10 polymorphisms and coronary artery lesions (CALs) in Kawasaki disease (KD) is limited. We investigated whether 3 IL-10 genetic polymorphisms (-1082 A/G, -819 T/C, and -592 A/C) are associated with development of CALs in KD. METHODS AND RESULTS: The genotyping of IL-10 polymorphisms was conducted for 279 KD children (172 without and 107 with CALs in acute stage). Thirty-three patients had CALs in chronic stage and 74 only with transient CALs. The homozygous variant genotype CC of IL-10-819 and IL-10-592 was associated with 80% (P=0.006) and 79% (P=0.008) reduction in risk of CALs in acute stage, respectively. The C allele of IL-10-819 and IL-10-592 was associated with 34% (P=0.034) and 33% (P=0.044) reduction in risk of CALs in acute stage, respectively. Compared with ATA haplotype (adjusted odds ratio (AOR) 0.63, P=0.029) or non-ACC haplotype (AOR 0.64, P=0.033), ACC haplotype was associated with a significantly reduced risk for CALs in acute stage, but not for CALs in chronic stage. Compared with non-ATA haplotype (AOR 1.53, P=0.034), ATA haplotype was associated with a significantly increased risk of CALs, except for CALs in the chronic stage. CONCLUSIONS: The effects of IL-10 gene polymorphism on CALs in acute KD are important. The persistence of CALs in chronic stage depends much more on other factors such as the times of intravenous immunoglobulin treatment.
Subject(s)
Alleles , Coronary Disease/genetics , Interleukin-10/genetics , Mucocutaneous Lymph Node Syndrome/genetics , Polymorphism, Genetic , Acute Disease , Child , Child, Preschool , Chronic Disease , Coronary Disease/drug therapy , Coronary Disease/pathology , Coronary Vessels/pathology , Female , Haplotypes , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunologic Factors/administration & dosage , Infant , Male , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/pathology , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Approximately 8-38% of children with Kawasaki disease (KD) will have persistent or recrudescent fever after initial intravenous immunoglobulin (IVIG) treatment and are at increased risk for development of coronary artery abnormalities. Using genetic markers may be helpful to identify the high-risk group of IVIG-resistant patients for aggressive treatment. The aim of this study was to evaluate the associations between 4 potential polymorphisms in the interleukin (IL)-1 family of genes and initial IVIG treatment failure in KD children. METHODS AND RESULTS: A total of 156 KD children (136 with and 20 without a response to IVIG treatment) who were treated with high-dose IVIG (2 g/kg) within 10 days of fever onset were recruited. Polymerase chain reaction and Taqman assays were used for genotyping. A significant increase in IVIG resistance risk was observed for IL-1B -511 TT and IL-1B -31 CC genotypes (adjusted odds ratio (AOR) 5.27, 95% confidence interval (CI) 1.69-16.38, P=0.004; AOR 3.95, 95%CI 1.26-12.41, P=0.019, separately). The diplotype TC/TC (at IL-1B -511 and -31) also showed a significantly increased risk of IVIG resistance (AOR 4.32, 95%CI 1.36-13.71, P=0.013). CONCLUSIONS: The IL-1B -511 TT and IL-1B -31 CC genotypes or the TC/TC diplotype may be associated with initial IVIG treatment failure in Taiwanese children with KD.
