2015 KSCPT 추계학술대회

Pharmacogenomic data analysis and interpretation

인제의대 약물유전체연구센터

• SNP genotyping method, genome browser, haplotype analysis, gene identification for disease or drug response
• Genetic variation (1%) - Major allele vs minor allele
• 1%이상이면 polymorphism, 미만이면 mutation이라고 한다.
• Non synonymous SNP - change가 없는 경우. SNP가 있더라도 aa. sequence의 변화가 항상 유발되는건 아니다.
• linkage disequilibrium - particular combination of variants are more likely to occur together than expected by chance - the result of physical proximity on a chromosome.
• SNP - also useful for GWAS.
• https://en.wikipedia.org/wiki/Genome-wide_association_study
• Genotyping techniques
  • Direct hybridization
  • PCR-based methods
    • TaqMan PCR assay https://en.wikipedia.org/wiki/TaqMan
  • Fragment analysis -
  • ligation assay
  • Primer extension Assay
  • Sequencing
• Genome Browser
  • NCBI
  • 1000genome br
  • UCSC br
  • Genecard
  • Ensembl
  • HapMap project
  • 한국인참조유전체 DB
• CYP2B6 - http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=3745274
• CYP2D6
  • CYP2D6*4 - https://www.pharmgkb.org/haplotype/PA165816579
  • CYP2D6*5 - https://www.pharmgkb.org/haplotype/PA165948092
  • CYP2D6*10 - https://www.pharmgkb.org/haplotype/PA165816582

과거자료

Tamox -(CYP2D6)-> Z-4 hydroxy Tamoxifen N-desmethyl-tamoxifen -(CYP2D6)-> endoxifen

Clinical benefit CYP2D6*10/10 Genotype이 treatment effect에 영향을 미친다. Shorter TTP in patients with CYP2D610/*10 than those with the other genotypes