rs11969064 - KIF13A - NHLRC1

Magnitude 4.5 · 1 study on file

Reported associations

  • Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease. - JAMA (2019) · Walker GJ, Harrison JW, Heap GA, Voskuil MD, Andersen V, Anderson CA, Ananthakrishnan AN, Barrett JC, Beaugerie L, Bewshea CM, Cole AT, Cummings FR, Daly MJ, Ellul P, Fedorak RN, Festen EAM, Florin TH, Gaya DR, Halfvarson J, Hart AL, Heerasing NM, Hendy P, Irving PM, Jones SE, Koskela J, Lindsay JO, Mansfield JC, McGovern D, Parkes M, Pollok RCG, Ramakrishnan S, Rampton DS, Rivas MA, Russell RK, Schultz M, Sebastian S, Seksik P, Singh A, So K, Sokol H, Subramaniam K, Todd A, Annese V, Weersma RK, Xavier R, Ward R, Weedon MN, Goodhand JR, Kennedy NA, Ahmad T · PubMed 30806694

    Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffecte


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Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • TPMT pharmacogenetic testing before thiopurine therapy Moderate

    rs11969064 is a TPMT cis-eQTL that reduces enzyme expression, impairing thiopurine metabolism and increasing toxicity risk

    Request TPMT genotyping prior to thiopurine initiation; discuss dose adjustment based on genotype

Screening

  • Myelosuppression symptoms if prescribed thiopurines Moderate

    Carriers of rs11969064 have increased myelosuppression risk during thiopurine therapy due to impaired drug metabolism

    Report unusual infections, severe bruising, or unexplained bleeding to your physician