PMID- 12783130 OWN - NLM STAT- MEDLINE DCOM- 20031002 LR - 20161013 IS - 0929-6646 (Print) IS - 0929-6646 (Linking) VI - 102 IP - 3 DP - 2003 Mar TI - Association between levels of TNF-alpha and TNF-alpha promoter -308 A/A polymorphism in children with Kawasaki disease. PG - 147-50 AB - BACKGROUND AND PURPOSE: 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. FAU - Chien, Yin-Hsiu AU - Chien YH AD - Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan. FAU - Chang, Kuei-Wen AU - Chang KW FAU - Yang, Yao-Hsu AU - Yang YH FAU - Lu, Meng-Yao AU - Lu MY FAU - Lin, Yu-Tsan AU - Lin YT FAU - Chiang, Bor-Luen AU - Chiang BL LA - eng PT - Journal Article PL - Singapore TA - J Formos Med Assoc JT - Journal of the Formosan Medical Association = Taiwan yi zhi JID - 9214933 RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Case-Control Studies MH - Child MH - Child, Preschool MH - Female MH - Gene Frequency MH - Humans MH - Infant MH - Male MH - Mucocutaneous Lymph Node Syndrome/*genetics MH - *Polymorphism, Genetic MH - Promoter Regions, Genetic/genetics MH - Receptors, Tumor Necrosis Factor/blood/*genetics MH - Tumor Necrosis Factor-alpha/analysis/*genetics EDAT- 2003/06/05 05:00 MHDA- 2003/10/03 05:00 CRDT- 2003/06/05 05:00 PHST- 2003/06/05 05:00 [pubmed] PHST- 2003/10/03 05:00 [medline] PHST- 2003/06/05 05:00 [entrez] PST - ppublish SO - J Formos Med Assoc. 2003 Mar;102(3):147-50.