Abstract 1001 Poster Session IV, Tuesday, 5/4 (poster 137)

TNF-α has been implicated in the pathogenesis of Kawasaki disease (KD). Genetic polymorphisms located in the promoter region of the TNF-α gene and in the first intron of the lymphotoxin α gene have been associated with increased secretion of TNF-α. We hypothesized that individuals with the high secretor genotype are predisposed to develop KD and the coronary aneurysms associated with this disease. Objective: To compare the genotypic frequencies at the +250 locus in the first intron of the lymphotoxin α gene and -308 locus in the TNF-α gene between Caucasian children with and without KD. Methods: A genotypic analysis was performed at two loci upstream from the TNF-α transcription start site using PCR amplification and restriction enzyme digestion. The genotypic frequencies in Caucasian children with KD were compared to a healthy Caucasian population and the mean values for 2 Japanese populations without KD from published studies. Results: The genotypic frequencies at the +250 and -308 loci are shown in the Table. The high secretor genotype at the +250 locus, A/A, was found at a higher frequency in Caucasian children with KD (Cau +KD) than healthy Caucasians without KD (Cau -KD) (0.62 vs 0.36, p < 0.01). In contrast, the high secretor genotype at the -308 locus, A/A, was not found at a higher frequency in Caucasian children with KD. However, the genotypic frequencies at this locus were very similar to genotypic frequencies of healthy Japanese populations (J -KD).

Table 1 No caption
Full size table

Conclusions: Caucasian children with KD have a higher frequency of the high secretor genotype at the +250 locus but not the high secretor genotype at the -308 locus. However, Caucasian children with KD are genotypically at the -308 locus very similar to the Japanese population, a population regarded as being at high risk for developing KD.

Supported by the Crippled Children's Foundation (MWQ)