We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

Kawasaki disease is a systemic vasculitis, mainly encountered in children. It may affect any organ. Acute cholestasis and severe obstructive jaundice is an atypical manifestation of the disease. We herein present two children with Kawasaki disease and severe direct hypebilibirunemia who also were homozygous and heterozygous respectively for the (TA)7 promoter polymorphism of Gilbert syndrome. Intravenous immunoglobulin was administered to both patients at the acute phase of the disease and the fever remitted within 24 hr following the immunoglobulin administration. Furthermore oral aspirin at a dose of 80-100 mg/kg/24 hr was also given. The first child did not develop any coronary ectasia or aneurysm, whereas dilation of the right coronary artery was identified in the second child, one month after the disease onset. We discuss the possible contribution of Gilbert syndrome to the development of jaundice in our patients.
Administration, Oral ; Aspirin/therapeutic use ; Child ; Child, Preschool ; Echocardiography ; Female ; Gilbert Disease/*complications/*diagnosis/genetics ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Jaundice/etiology ; Male ; Mucocutaneous Lymph Node Syndrome/*complications/*diagnosis/drug therapy ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Sequence Analysis, DNA

Antibodies, Monoclonal ; therapeutic use ; Drug Resistance ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infliximab ; Mucocutaneous Lymph Node Syndrome ; diagnosis ; drug therapy ; Plasma Exchange ; Tumor Necrosis Factor-alpha ; genetics

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