Tissue inhibitor of metalloproteinase 2 and coronary artery lesions in Kawasaki disease

Abstract

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).

Study design: 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.