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Page 244 Abaji et al. Cancer Drug Resist 2019;2:242-55 I http://dx.doi.org/10.20517/cdr.2018.24

Table 1. This table summarizes the prominent studies in the literature which investigated the pharmacogenetics of
asparaginase and highlights the most important finding
Discovery Internal
Study Method Gene Polymorphism Toxicity cohort (n) validation Validated Notes and conclusions
cohort (n)
Chen et al. [25] GWAS GRIA1 rs4958351 HSRs 322 163 Yes rs4958351 had the strongest
2010 association in the original
study (Chen et al. [25] 2010).
Carriers of the minor allele
were at increased risk of
[31]
Rajic et al. Gene- rs10070447 developing HSRs to ASNase.
2015 Candidate
The associations of the
rs6890057 variants with increased risk
of HSRs found in the original
study were successfully
[31]
replicated by (Rajic et al.
[9]
Kutszegi et al. Gene- rs4958676 2015, n = 146) but not by
[9]
2015 Candidate rs6889909 (Kutszegi et al. 2015,
n = 505)
Fernandez et al. Gene- HLA-DRB1 HLA-DRB1 HSRs 541 1329 Yes The variant allele was
[4]
2014 Candidate *07:01 associated with an increased
risk of ASNase HSR
Alleles that confer high-
affinity binding to ASNase
epitopes contribute to the
observed higher frequency of
HSRs
Fernandez et al. [30] GWAS HLA-DRB1 rs17885382 HSRs 3308 No N/A The variant allele was
2015 associated with an increased
risk of ASNase induced HSR
and is in almost perfect
linkage disequilibrium with
HLA-DRB1*07:01 found in a
previous study
NFATC2 rs6021191 The variant is associated
with an increased risk of
ASNase HSR
[10]
Ben Tanfous et al. Gene- ASNS rs3832526 Allergy 285 248 Yes Patients homozygous for
2015 Candidate the triple repeat allele (3R)
had the complications
more frequently than other
genotype groups
Pancreatitis No ASNS haplotype *1
harbouring double repeat
(2R) allele conferred a
protective effect from these
toxicities
Abaji et al. 2017 EWAS MYBBP1A rs3809849 Pancreatitis 302 282 Yes This variant was also
[41]
associated with allergy,
thrombosis, event-free
survival and overall survival
IL16 rs11556218 Yes This variant was also
associated with thrombosis
SPEF2 rs34708521 Yes This variant was also
associated with thrombosis
[15]
Wolthers et al. GWAS ULK2 rs281366 Pancreatitis 700 No N/A 14 of the 27 associations
2017 found in the study were of
polymorphisms in ULK2 gene
RGS6 rs17179470 The variant in RGS6 gene
was associated with
pancreatitis in patients less
than 10 years old
The risk of pancreatitis
associated with carrying the
risk alleles of rs281366 and
rs17179470 was additive in
patients less than 10 years
old