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).

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