Development of a simple genotyping method for the HLA-A*31:01-tagging SNP in Japanese

Pharmacogenomics. 2015;16(15):1689-99. doi: 10.2217/pgs.15.115. Epub 2015 Oct 2.

Abstract

Aim: To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Materials & methods: DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay.

Results: HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays.

Conclusion: Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.

Keywords: PCR-RFLP; Stevens–Johnson syndrome/toxic epidermal necrolysis; carbamazepine; screening test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / adverse effects
  • Asian People / genetics*
  • Carbamazepine / adverse effects
  • DNA / genetics
  • Gene Frequency
  • Genetic Markers
  • Genotype
  • HLA-A Antigens / genetics*
  • Humans
  • Japan
  • Linkage Disequilibrium
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Stevens-Johnson Syndrome / epidemiology
  • Stevens-Johnson Syndrome / genetics*
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Genetic Markers
  • HLA-A Antigens
  • HLA-A31 antigen
  • Carbamazepine
  • DNA