Increased Frequency of Alleles Associated with Elevated Tumor Necrosis Factor-α Levels in Children with Kawasaki Disease

Tumor Necrosis Factor-α Allele Lymphotoxin-α+250 Is Associated with the Presence and Severity of Placental Inflammation among Preterm Births

“…Quasney et al (24) found an increased frequency of the AA genotype of LT-␣ϩ250 among white children with Kawasaki disease compared with healthy control subjects. The AA genotype of LT-␣ϩ250 was associated with more severe psoriasis (26) and higher rate of mortality among children with bacteremia (27) and septic adults (22).…”

“…Reports on the possible role of TNF-␣Ϫ308 and TNF-␣Ϫ238 on susceptibility and severity of diseases involving the innate immune system have yielded conflicting results. The A allele of TNF-␣Ϫ308 occurred more often among children who had Kawasaki disease and developed coronary artery abnormalities (24). Carriage of the A allele of TNF-␣Ϫ308 was associated with worse outcome among patients with cerebral malaria (30), leishmaniasis (31), and severe sepsis (32) but had no effect on the susceptibility to or severity of rheumatoid arthritis (33), multiple sclerosis (34), or Crohn disease (35).…”

“…DNA was extracted using the Genomic DNA purification Kit (Promega, Madison, WI, U.S.A.). Genotypic analysis for TNF-␣ polymorphic sites was performed using a PCR-restriction fragment length polymorphism technique, as previously described (22)(23)(24).…”

Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine

“…30 Although several other groups have studied other combinations of HLA subtypes, no consistent association has been detected so far. Considering that no significant linkage was detected near the 6p region in our genome-wide linkage analysis, 31 34 and MCP-1 35 ), hematopoietins (interleukin-4 (IL-4) [36][37][38] and IL-6 39 ), IL-1 family (IL-1b, 37 IL-18, 40 and IL-1Ra 37 ), IL-10 family (IL-10 41 ), platelet-derived growth factor family (vascular endothelial growth factor (VEGF) [42][43][44][45] and VEGFR2 42 ), and tumor necrosis factor (TNF) family (TNF-a, 46-50 lipoteichoic acid, 47 and CD40L 51,52 ). Other candidates include plasma proteins (C-reactive protein [53][54][55] and MBL2 53,55,56 ), matrix metalloproteinase (MMP) and their inhibitors (MMP2, 58 MMP3, 57,58 MMP-9, 58 MMP-12, 58 MMP-13, 58 and tissue inhibitors of metalloproteinase-2 59 ), enzymes related to atherosclerosis (methylenetetrahydrofolate reductase (MTHFR), 60 endothelial nitric oxide synthase, 61 and inducible nitric oxide synthase 61 ), components of the renin-angiotensin system (angiotensin-converting enzyme [62][63][64][65] and AGTR1 64 ), and an unclassified group (CD14, 66 FCGR2A, 67,68 SLC11A1, 69 PLA2G7, 70 UGT1A1, 71 MICA, 72 and HMOX1 71 ).…”

Genetic polymorphisms in Kawasaki disease

“…Interestingly, some results have indicated that the genetic association was observed only with susceptibility, not with CAL formation. However, other studies have revealed inconsistent results (Table 1) [45][46][47][48][49][50][51][52][53][54][55][56][57] . These results indicate that the genes responsible for susceptibility and CAL formation may be different between populations [7,32,37,38,[58][59][60] .…”