Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb;187(1):145-153.
doi: 10.1007/s11845-017-1608-x. Epub 2017 May 3.

Association of NUDT15 c.415C>T allele and thiopurine-induced leukocytopenia in Asians: a systematic review and meta-analysis

A L Zhang  1 , J Yang  1 , H Wang  1 , J L Lu  1 , S Tang  1 , X J Zhang  2
Affiliations
Review

Association of NUDT15 c.415C>T allele and thiopurine-induced leukocytopenia in Asians: a systematic review and meta-analysis

A L Zhang et al. Ir J Med Sci. 2018 Feb.

Abstract

Background: Thiopurines, commonly used to treat autoimmune conditions and cancer, can be limited by life-threatening leucopenia. However, whether NUDT15 (nucleoside diphosphate-linked moiety X-type motif 15) is associated with thiopurine-induced leucopenia in Asians is controversial.

Methods: Relevant studies in English that were published until July 10, 2016 were identified through PubMed, EMbase, and other web knowledge databases. Study quality was assessed according to the Newcastle-Ottawa Scale (NOS) criteria. Summary risk ratio (RR) and 95% confidence intervals (CI) were estimated based on a fixed-effects model or a random-effects model, depending on the absence or presence of significant heterogeneity.

Results: Seven studies of 1138 patients met our inclusion criteria. Random-effects model meta-analysis provided evidence that T carriers of NUDT15 c.415C>T were significantly correlated with high incidences of thiopurine-induced leukocytopenia [CT + TT vs. CC: RR = 3.79, 95%CI (2.64 ~ 5.44), P < 0.00001]. This correlation was especially strong in TT patients, where it was found to be significantly increased by 6.54-fold compared with CC patients [TT vs. CC: RR = 6.54, 95%CI (3.34 ~ 12.82), P < 0.00001]. We also found that the NUDT15 c.415C>T variant was common in Asians and Hispanics, but rare in Europeans and Africans; the frequency of the NUDT15 c.415C>T distribution varied substantially by race/ethnicity.

Conclusion: The results of this meta-analysis confirm that NUDT15 c.415C>T may be an important predictor of thiopurine-induced leukocytopenia in Asians. Genotype targeting of NUDT15 c.415C>T before initiating thiopurine treatment may be useful to limit leukocytopenia.

Keywords: Asians; Leukocytopenia; NUDT15 c.415C>T; Thiopurines.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Br J Haematol. 2015 Oct;171(1):109-15 - PubMed
    1. Haematologica. 2016 Jan;101(1):e24-6 - PubMed
    1. J Clin Pharmacol. 2013 Jun;53(6):670-4 - PubMed
    1. J Pediatr. 1991 Dec;119(6):985-9 - PubMed
    1. J Gastroenterol. 2016 Jan;51(1):22-9 - PubMed

LinkOut - more resources