A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid

Human arylamine N-acetyltransferase (NAT) activity is determined by two distinct genes, NAT1 and NAT2, and the classical acetylation polymorphism in NAT2 has been associated with a variety of disorders, including lupus erythematosus and arylamine induced cancers. Over 50% of the white population exhibit a slow acetylator phenotype. The genetic basis of the defect has been identified and several DNA based assays are available for genotyping studies. We present here a simplified, rapid PCR based assay for the identification of the major slow acetylator genotypes and validate it using isoniazid as probe drug. This assay was 100% predictive of phenotype. The three genotypes (homozygous mutated, heterozygous, and homozygous rapid) corresponded to a trimodal distribution of Ac-INH/INH metabolic ratios (slow, intermediate, and rapid) without overlapping.

Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel (author)
Gough, A.C. (author)
Harrison, D.J. (author)
Wolf, C.R. (author)
Rane, AndersUppsala universitet,Institutionen för medicinska vetenskaper,Klinisk farmakologi, A Rane (author)
Uppsala universitetKlinisk farmakogenomik och osteoporos (creator_code:org_t)

By the author/editor: Smith, C.A.; Wadelius, Mia; Gough, A.C.; Harrison, D.J.; Wolf, C.R.; Rane, Anders

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