Highlights
- •Genetic variance of TPMT is not a determinant for AZA-induced leukopenia in Korea
- •In Korea, the NUDT15 p.R139C variant is common and may predict AZA-induced leukopenia
- •Also, this variant of homozygote primarily serves as a risk factor for early rather than late-developing leukopenia of severe grade, along with the associated alopecia.
Abstract
Azathioprine (AZA)-induced leukopenia is a relatively common complication in Korean
patients. In addition to variation in TPMT (thiopurine S-methyltransferase), the NUDT15 p.R139C variant was recently identified to have a strong association with AZA-induced
leukopenia. We investigated these associations in Korean patients undergoing AZA treatment
with various neurological diseases. Among 84 enrolled patients, 20 (23.8%; 7 early,
13 late) exhibited leukopenia. The NUDT15 p.R139C variant was associated with leukopenia (OR: 11.844, 95% CI 3.984–36.024,
p = 1.327 × 10−5). The allelic frequency of NUDT15 p.R139C was as high as 10.7% and the frequency of the C/C, C/T, and T/T genotypes
was 84.5, 10.7, and 5.9%, respectively. All T/T homozygous patients (5/5) developed
early severe-grade leukopenia (white blood cells <1000 mm−3) and severe alopecia. NUDT15 p.R139C was strongly associated with early leukopenia and severe alopecia (OR for
early leukopenia: 107.624, 95% CI 18.857–614.250, p = 1.403 × 10−7, OR for severe alopecia: 77.152, 95% CI 17.378–342.526, p = 1.101 × 10−8). The sensitivity and specificity for predicting AZA-induced early leukopenia were
85.7% and 92.2%, respectively. Therefore, the NUDT15 p.R139C variant is common and strongly associated with AZA-induced early leukopenia
and severe alopecia in Korean patients with various neurological diseases.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: April 26, 2017
Accepted:
April 25,
2017
Received in revised form:
April 21,
2017
Received:
December 27,
2016
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
