Tissue inhibitor of metalloproteinase 2 and coronary artery lesions in Kawasaki disease.
OBJECTIVE
To identify cytokine genes uniquely expressed in peripheral blood mononuclear cells (PBMNCs) in the acute phase of Kawasaki disease (KD) with coronary artery lesions (CALs).


METHODS
We screened the mRNA expression levels of PBMNCs from 4 pairs of KD patients with and without CAL using DNA microarray. The result was confirmed by real-time polymerase chain reaction (RT-PCR). The genetic association study was performed to analyze the significance of single nucleotide polymorphisms in the identified gene for the development of CAL in KD patients (184 controls, 144 KD patients with CAL, 64 KD patients without CAL).


RESULTS
The microarray analysis showed that tissue inhibitor of metalloproteinases 2 (TIMP2) was expressed at higher levels in PBMNCs of KD patients with CAL than in KD patients without CAL. Quantitative RT-PCR confirmed that the expression levels were significantly higher in the KD patients with CAL than in those without CAL (P < .05). Among KD patients, TIMP2 promoter polymorphisms were significantly associated with a risk of CAL (P < .01). There was a significant difference in the transcriptional activities between the haplotypes of the TIMP2 promoter polymorphisms by reporter assay using U-937.


CONCLUSIONS
TIMP2 overexpression and the promoter polymorphisms might play a role in the development of CALs.
Furuno
Kenji
K
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. furuken@pediatr.med.kyushu-u.ac.jp <furuken@pediatr.med.kyushu-u.ac.jp>
Takada
Hidetoshi
H
Yamamoto
Ken
K
Ikeda
Kazuyuki
K
Ohno
Takuro
T
Khajoee
Vahid
V
Mizuno
Yumi
Y
Hara
Toshiro
T
D000208:Acute Disease; D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D003327:Coronary Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012333:RNA, Messenger; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2