title: Genetic polymorphism of SMAD5 is associated with Kawasaki disease.
abstract: Mothers against decapentaplegic homolog (SMAD) proteins are intracellular mediators of members of the transforming growth factor-β (TGF-β) superfamily, which are activated by bone morphogenetic proteins (BMPs). On activation, SMAD5 forms heterometric SMAD complexes, which are translated to the nucleus where they regulate gene transcription. TGF-β induces T cell activation and cardiovascular disease, two important features of Kawasaki disease (KD), whereas BMP is associated with coronary artery disease. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) of SMAD5 may be associated with KD and coronary arterial lesions (CALs). Genotyping for 15 SNPs of the SMAD5 gene (rs3764941, rs10085013, rs6596284, rs7356756, rs13179769, rs13166063, rs1109158, rs4585442, rs4146185, rs12719481, rs6865297, rs3206634, rs6871224, rs1057898, and rs7031) was performed by direct sequencing of 105 KD patients and 303 healthy adult controls. We also compared the allele frequencies between a CAL group (n = 31) and a normal coronary group (n = 74). Results showed that among the 15 SNPs, rs3206634 was significantly associated with KD in a recessive model (odds ratio = 2.31, p = 0.019), whereas there was no association between any of the 15 SNPs and CALs. These findings may be used as a risk factors development of KD or for future generations of therapeutic treatments for KD.
authors.affiliation: Department of Pediatrics, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gandong-gu, Seoul, 137-727, Korea.
authors.forename: Ja Hyang
authors.initials: JH
authors.lastname: Cho
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Han
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Cha
authors.forename: Joo Ho
authors.initials: JH
authors.lastname: Jung
authors.forename: Kyung Lim
authors.initials: KL
authors.lastname: Yoon
mesh_terms: D000328:Adult; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D051902:Smad5 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C497797:SMAD5 protein, human; D051902:Smad5 Protein; D004247:DNA