Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled. ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05). In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without. ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations.
*Polymorphism, Genetic ; Peptidyl-Dipeptidase A/*genetics ; Mucocutaneous Lymph Node Syndrome/*enzymology/*genetics/pathology ; Male ; Infant ; Humans ; Genotype ; Gene Frequency ; Female ; Dilatation, Pathologic ; Coronary Vessels/pathology ; Child, Preschool ; Case-Control Studies ; Alleles

OBJECTIVEKawasaki disease (KD) is an acute and self-limited systemic vasculitis syndrome of unknown origin that mainly affects small and medium-sized arteries, particularly the coronary arteries, which is followed by aneurysm formation. Increased levels of matrix metalloproteinase-1 (MMP-1) have been detected in aortic aneurysms in adults, suggesting an important role of MMP-1 in arterial wall destruction and resultant aneurysm formation. The aim of this study was to investigate the potential role of MMP-1 in the pathogenesis of coronary artery lesions in patients with KD.

METHODSForty patients with KD, including 23 patients without coronary artery lesions (CAL) and 17 patients with CAL, as well as age-matched 10 febrile and 10 healthy afebrile controls were studied. The duration of KD was divided into three phases: the acute phase, the subacute phase and the convalescent phase. Enzyme-linked immunosorbent assay was used to detect the protein levels of MMP-1 in the sera. MMP-1 mRNA expression in the circulating leucocytes was studied using reverse transcription-polymerase chain reaction.

RESULTSLevels of MMP-1 protein in serum and MMP-1 mRNA expression in the leucocytes were significantly elevated at the acute phase in the two groups of KD patients (CAL group: 14.91 +/- 3.88 ng/ml and 0.89 +/- 0.15 ng/ml; NO-CAL group: 11.27 +/- 3.28 ng/ml and 0.77 +/- 0.14, respectively), compared with febrile (7.05 +/- 1.98 ng/ml and 0.45 +/- 0.12 ng/ml, respectively) and afebrile (5.13 +/- 1.20 ng/ml and 0.29 +/- 0.12 ng/ml, respectively) controls (P < 0.01). Furthermore, MMP-1 protein and MMP-1 mRNA levels were significantly higher in KD patients with CAL than in KD patients without CAL (P < 0.05). There was a significantly positive correlation between the serum protein level of MMP-1 at the acute phase of KD and the circulating leucocytes counts (r = 0.750, P < 0.01). The MMP-1 serum protein level and mRNA expression in the leucocytes at the acute phase of the two KD groups decreased obviously from the subacute through the convalescent phases (P < 0.05 or P < 0.01).

CONCLUSIONThe expression of MMP-1 at the acute phase of KD was significantly elevated, especially in KD patients with CAL. MMP-1 might be involved in the formation of coronary artery lesions and pathogenesis of KD.

Acute Disease ; Child, Preschool ; Coronary Aneurysm ; enzymology ; etiology ; pathology ; Coronary Vessels ; pathology ; Enzyme-Linked Immunosorbent Assay ; Fever ; etiology ; Humans ; Infant ; Leukocytes ; enzymology ; Male ; Matrix Metalloproteinase 1 ; blood ; genetics ; Mucocutaneous Lymph Node Syndrome ; complications ; diagnosis ; RNA, Messenger ; blood ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index