Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

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Citation

Lin HJ, Probst-Hensch NM, Hughes NC, Sakamoto GT, Louie AD, Kau IH, Lin BK, Lee DB, Lin J, Frankl HD, Lee ER, Hardy S, Grant DM, Haile RW

Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

Pharmacogenetics. 1998 Jun;8(3):269-81.

PubMed ID
9682272 [ View in PubMed
]
Abstract

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens. Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may provide indirect support for a heterocyclic amine mechanism. We used single strand conformation polymorphism and heteroduplex analysis to screen fro mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer. Thirteen different single-base mutations were found: C97T, C190T, T402C, G445A-G459A-T640G ( a combination of three mutations), C559T, G560A, A613G, A752T, T777C, G781A, and A787G. Function of novel mutations was tested by bacterial production of enzymes and measurements of Km, Vmax, and stability. However, on 24-control individuals and 18 cases carried an inactivating NAT1 mutation. When combined with our data on the NAT2 acetylation polymorphism, we saw no evidence for an association between N-acetyltransferases and prevalence of adenomas. Larger sample sizes are required for further evaluation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Arylamine N-acetyltransferase 1P18440Details