Related Experiment Video

Updated: Jun 13, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

Common variants in CASP3 confer susceptibility to Kawasaki disease

Yoshihiro Onouchi1, Kouichi Ozaki, Jane C Buns

  • 1Laboratory for Cardiovascular diseases, Center for Genomic Medicine RIKEN, Yokohama 230-0045, Japan. onouchi@src.riken.jp

Human Molecular Genetics
|April 29, 2010
PubMed

Insights

Genetic variants in the caspase-3 gene (CASP3) are linked to Kawasaki disease (KD) susceptibility in children. A specific CASP3 variant affects immune cell gene expression, influencing KD risk.

Area of Science:

  • Genetics
  • Immunology
  • Pediatrics

Background:

  • Kawasaki disease (KD) is an acute vasculitis affecting children's arteries.
  • Host genetics are implicated in KD pathogenesis.
  • The specific genetic factors contributing to KD remain largely unknown.

Purpose of the Study:

  • To investigate the association between genetic variants and Kawasaki disease susceptibility.
  • To identify specific genes and mutations conferring risk for KD.
  • To elucidate the functional impact of identified variants on gene expression.

Main Methods:

  • Case-control study comparing genetic variants in KD patients and controls.
  • Genotyping of single nucleotide polymorphisms (SNPs) in the caspase-3 gene (CASP3).
  • Analysis of SNP association with KD in Japanese and European American cohorts.
  • Functional assays to assess the impact of a specific SNP on transcription factor binding.

Main Results:

  • Multiple CASP3 variants in linkage disequilibrium were associated with KD susceptibility in both Japanese and European American cohorts.
  • A specific G to A substitution (rs72689236) in the 5' untranslated region of CASP3 was significantly associated with KD.
  • This SNP abolished the binding of nuclear factor of activated T cells (NFAT) to the regulatory DNA sequence.

Conclusions:

  • Genetic variations in CASP3 contribute to Kawasaki disease susceptibility.
  • Altered CASP3 expression due to these variants may influence KD pathogenesis.
  • These findings highlight the role of CASP3 in immune effector cells in KD development.

More Related Videos

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes11:33

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.