A polymorphism in plasma platelet-activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease.
OBJECTIVE
To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD).


METHODS
The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele-specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]-acetyl-PAF.


RESULTS
There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) +TT (homozygous deficient) group required additional IVIG (52% vs 14%, P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P <.0001).


CONCLUSIONS
We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.
Minami
Takaomi
T
Department of Pediatrics, Wakayama Medical University, Wakayama, Japan. takaomi@wakayama-med.ac.jp
Suzuki
Hiroyuki
H
Takeuchi
Takashi
T
Uemura
Shigeru
S
Sugatani
Junko
J
Yoshikawa
Norishige
N
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric
D016756:Immunoglobulins, Intravenous; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase