IDENTIFICATION AND PREVALENCE STUDY OF 17 ALLELIC VARIANTS OF THE HUMAN NAT2 GENE IN A WHITE-POPULATION

The prevalence and distribution of seven point mutations at the coding region of the highly polymorphic NAT2 gene were studied in 1008 chrom osomes from healthy Spanish subjects. Most of the genes studied (78.4% ) had one or more mutations, distributed in seventeen allelic variants of the NAT2 gene. Three alleles were present at high frequencies, nam ely NAT25B (41.6%), NAT2*6A (23.6%) and NAT2*4 (21.6%). The frequenci es for the rest of alleles were: NAT212A (2.5%), NAT2*6B (2.0%), NAT2 13 (1.9%), NAT2*5A (1.5%), NAT2*7B (1.2%), NAT2*12C (1.0%), NAT2*5C ( 0.8%), NAT214C (0.8%), NAT2*14A (0.6%), NAT2*5D (0.3%), NAT2*12B (0.2 %), and NAT214D (0.1%). In addition, we identified two new allelic va riants with mutations at 191A+341C+803G (0.1%) and 282T+590A+803G (0.3 %) which to our knowledge are described here for the first time. No ot her combination of mutations was identified, including the previously described allelic variants NAT214B, NAT2*14E, NAT2*5E and NAT2*7A. Th e phenotype predictive capacity of simplified PCR tests including anal yses for mutations at 341C and 590A, and more sophisticated tests anal ysing seven mutations revealed that, in the population studied, the an alysis of these two mutations is enough to predict as rapid acetylator s over 99.5% subjects with two rapid genes, and about 94% subjects wit h one rapid gene. Given a prevalence of poor acetylators of about 55% subjects, the simplified analysis would predict the phenotype in about 97.5% subjects.