Association between levels of TNF-alpha and TNF-alpha promoter -308 A/A polymorphism in children with Kawasaki disease.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) has been shown to play a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). We investigated the serum levels of TNF-alpha and soluble TNF receptor 1 (STNFR1) levels, and genetic polymorphisms of the TNF-alpha 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-alpha and STNFR1 were assayed by enzyme-linked immnosorbent assay, and DNA polymorphisms of the 5' flanking region of TNF-alpha 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-alpha 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-alpha 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-alpha 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-alpha and STNFR1 were found in KD patients but there was no correlation between these levels. The relationship between the pathogenesis of KD and TNF-alpha gene promoter -308G to A mutation towards cytokine production remains to be clarified.
Chien
Yin-Hsiu
YH
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan.
Chang
Kuei-Wen
KW
Yang
Yao-Hsu
YH
Lu
Meng-Yao
MY
Lin
Yu-Tsan
YT
Chiang
Bor-Luen
BL
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha