Pharmacogenomics

TPMT and NUDT15

TRTPMT ve NUDT15

Two enzymes whose genetic deficiency reduces inactivation of thiopurine drugs, causing excess active metabolite accumulation and a markedly increased risk of severe myelosuppression.

In depth

Thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) act on separate steps of thiopurine metabolism, and either poor-function genotype independently raises thioguanine nucleotide levels from azathioprine, mercaptopurine, or thioguanine, increasing the risk of life-threatening neutropenia. NUDT15 deficiency is more common in East Asian and Hispanic populations, while TPMT deficiency is better documented in European populations.

CPIC combines TPMT and NUDT15 phenotype into a single actionable category and recommends substantial starting-dose reduction, with closer blood-count monitoring, in patients who are intermediate or poor metabolizers for either enzyme; normal-function patients receive standard starting doses.

Clinical pearl

Test both TPMT and NUDT15 before starting a thiopurine where feasible, since either deficiency alone is sufficient to cause severe, potentially fatal myelosuppression at standard doses.

Example drugs

Azathioprine Mercaptopurine thioguanine
TRIn Turkish

TPMT ve NUDT15

Genetik eksikliği, tiyopürin ilaçlarının inaktivasyonunu azaltarak aşırı aktif metabolit birikimine ve belirgin şekilde artmış ağır miyelosüpresyon riskine yol açan iki enzimdir.

Tiyopürin S-metiltransferaz (TPMT) ve nudiks hidrolaz 15 (NUDT15), tiyopürin metabolizmasının ayrı basamaklarında görev alır; her iki enzimden birindeki zayıf işlevli genotip bile azatiyopürin, merkaptopurin veya tiyoguaninden oluşan tiyoguanin nükleotid düzeylerini bağımsız olarak yükselterek hayatı tehdit eden nötropeni riskini artırır. NUDT15 eksikliği Doğu Asya ve Hispanik toplumlarda daha yaygınken, TPMT eksikliği Avrupa toplumlarında daha iyi belgelenmiştir.

CPIC, TPMT ve NUDT15 fenotiplerini tek bir eyleme dönüştürülebilir kategoride birleştirir ve iki enzimden herhangi birinde ara veya zayıf metabolizör olan hastalarda, daha yakın kan sayımı izlemiyle birlikte, belirgin bir başlangıç dozu azaltımı önerir; normal işlevli hastalar standart başlangıç dozunu alır.

Mümkünse bir tiyopürine başlamadan önce hem TPMT hem NUDT15 test edilmelidir; çünkü ikisinden yalnızca birindeki eksiklik bile standart dozlarda ağır, ölümcül olabilecek miyelosüpresyona yol açabilir.

Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

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