Association between levels of TNF-α and TNF-α promoter - 308 A/A polymorphism in children with kawasaki disease
Journal
Journal of the Formosan Medical Association
Journal Volume
102
Journal Issue
3
Pages
147-150
Date Issued
2003
Author(s)
Abstract
Background and Purpose: Tumor necrosis factor-alpha (TNF-α) has been shown to play a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). We investigated the serum levels of TNF-α and soluble TNF receptor 1 (STNFR1) levels, and genetic polymorphisms of the TNF-α promoter gene in children with KD to delineate the genetic basis of KD. Methods: A total of 18 children (12 boys and 6 girls) with KD were studied, 9 of whom had the complication of coronary artery lesion (CAL) within 30 days after the onset of symptoms. Serum levels of TNF-α and STNFR1 were assayed by enzyme-linked immnosorbent assay, and DNA polymorphisms of the 5′ flanking region of TNF-α promoter gene at position -308 [guanine (G) to adenine (A)] and -238 (G to A) were studied by direct nucleotide sequencing. Results: The serum TNF-α level in KD patients was 113 ± 209.9 pg/mL (range, 2.0 to 756.9 pg/mL; median, 24.7 pg/mL; normal, < 10 pg/mL). The serum levels of STNFR1 in KD (4255 ± 2425 pg/mL) were higher than those of the control group (160 ± 116 pg/mL). Allele frequencies of -308A and -238A were 11.1% and 0% in the KD patients, and 0% and 3.1% in the control group. Neither TNF-α promoter polymorphism nor any significant risk factor for CAL was identified in KD patients. One patient, who was homozygous for -308A, showed the highest TNF-α level and elevated STNFR1 level but had no evidence of CAL. Positive correlations were found between serum levels of STNFR1 and C-reactive protein (r = 0.731, p = 0.007), and between STNFR1 and leukocyte counts at admission (r = 0.620, p = 0.008). Conclusions: Increased serum levels of TNF-α and STNFR1 were found in KD patients but there was no correlation between these levels. The relationship between the pathogenesis of KD and TNF-α gene promoter -308G to A mutation towards cytokine production remains to be clarified.
SDGs
Other Subjects
adenine; C reactive protein; cytokine; DNA; guanine; tumor necrosis factor alpha; tumor necrosis factor receptor 1; article; child; clinical article; controlled study; coronary artery disease; correlation analysis; cytokine production; DNA flanking region; DNA polymorphism; enzyme linked immunosorbent assay; female; gene frequency; gene mutation; genetic analysis; genetic polymorphism; homozygosity; hospital admission; human; infant; leukocyte count; male; mucocutaneous lymph node syndrome; nucleotide sequence; pathogenesis; promoter region; risk factor; symptom; Case-Control Studies; Child; Child, Preschool; Female; Gene Frequency; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Polymorphism, Genetic; Promoter Regions (Genetics); Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha
Type
journal article