Genotyping of the c.1423C>T (p.P475S) polymorphism in the ADAMTS13 gene by APLP and HRM assays: Northeastern Asian origin of the mutant

•The p.P475S polymorphism in the ADAMTS13 gene was investigated in 2500 samples.•Two new techniques based on APLP and HRM assays were developed.•The mutant allele is characteristic of northern East Asians.•The mutant is useful as an ancestry-informative allele.•The methods are useful to investigate an association with aortic dissection.

ADAMTS13 is a von Willebrand factor-cleaving protease. The mutant types of p.P475S (c.1423C>T) polymorphism in ADAMTS13 have a reduced activity in comparison with the wild type. In the present study, we investigated the frequency of the C-to-T substitution in 2584 genomic DNA samples from 25 Asian, European, and African populations using APLP (amplified product length polymorphism) and/or HRM (high-resolution melting) assays. Allele T (ADAMTS13∗T) was detected only in Asian populations and its frequency was observed to decrease gradually from north to south in 24 East Asian populations. Almost all ADAMTS13∗T were associated with ABO∗O. These results suggested that ADAMTS13∗T had occurred on a chromosome with ABO∗O in a northern part of East Asia. This SNP is useful as an ancestry-informative marker, and the present genotyping techniques are applicable to the investigation of an association between this SNP and aortic dissection (Kobayashi et al., 2012).

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (91 K)Download as PowerPoint slide