Prevalence of polymorphisms in thiopurine metabolism and association with adverse outcomes: a South Asian region-specific systematic review and meta-analysis

ABSTRACT

Background: Prevalence and impact of thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) minor allele frequencies in South Asian population is unclear.

Methods: We searched PubMed and Embase with keywords-TPMT and NUDT15 combined with South Asian countries. We included studies reporting frequency of TPMT and NUDT15 polymorphisms. We estimated the pooled prevalence of TPMT and NUDT15 polymorphisms and their impact on pooled odds ratio of adverse events with thiopurines.

Results: We included 26 studies in our analysis. The pooled prevalence of NUDT15 and TPMT polymorphisms was 16.5% (95% CI: 13.09–20.58) and 4.57% (95% CI: 3.66–5.68), respectively. In patients with adverse effects, the pooled prevalence of NUDT15 and TPMT polymorphism was 49.51% (95% C.I. 21.69–77.64) and 9.47% (95% C.I. 5.39–16.11), respectively. The odds ratio (OR) of adverse events with presence of TPMT polymorphisms was 3.65 (95% C.I., 1.43–9.28). The pooled OR for adverse events in presence of NUDT15 polymorphism was 12.63 (95% C.I., 3.68–43.26).

Conclusion: NUDT15 were reported more frequently than the TPMT polymorphisms in South Asian population and were more frequently associated with adverse events. These findings may have implications for preemptive testing amongst South Asian population and immigrants prior to starting thiopurines.

KEYWORDS:

• Inflammatory bowel disease
• azathioprine
• 6-mercaptopurine
• ulcerative colitis
• autoimmune hepatitis
• lymphoma
• Crohn’s disease

Author contributions

Study Design: V. Sharma, A. Jena, A. Patil, P. Bhatia

Search: D.K. Jha, V. Sharma,

Screening: D.K. Jha, A. Jena,

Data Extraction: A. Jena, S. Mishra, A.K. Singh

Data Validation: D. Sarwal, V. Sharma

RoB: A. Patil, A. Kumar, K.S. Kasudhan

Statistical Analysis: P. Kumar-M

Initial Draft: A. Jena, A. Patil, P. Kumar-M, V. Sharma

Important intellectual intent: P. Bhatia, A. Patil, V. Sharma

Final Review and approval: All authors

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This paper was not funded.