|(A;A)||3.5||incapable of detoxifying byproducts of certain drugs|
|(A;G)||3||(TPMT*3B) impaired drug metabolism|
The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the rs1142345(G) SNP, the allele is actually a TPMT*3A allele (OMIM).
The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment.
|Disease||Thiopurine methyltransferase deficiency|
|CLNDBN||Thiopurine methyltransferase deficiency|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
[PMID 17366837] Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada.
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 18662289] Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.
[PMID 18685564] Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.
[PMID 22385887] High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.
|qualified_impact||Low clinical importance, Likely pharmacogenetic|
|summary||Usually this variant is found in combination Y240C, forming the TPMT*3A variant. When alone, this variant produces the *3B variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity. Inability to metabolize thiopurine drugs can lead to severe adverse reactions. Heterozygotes may be advised to take a reduced dosage due to reduced metabolism of the drug.|
[PMID 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.