NAT2 Alleles

Since the human NAT2 locus was established as the site of the classical acetylation polymorphism, the study of NAT2 allelic variation has been an area of intense investigation. To date, 36 different NAT2 alleles have been detected in human populations.[3] Each of the variant alleles is composed of between one and four nucleotide substitutions, of which 16 have been identified, located in the protein-coding region of the gene. The correlation between NAT2 genotype and phenotype is well established. Moreover, there is a gene-dosage effect. Individuals who are homozygous for slow NAT2 alleles have a slow acetylator phenotype, individuals heterozygous for slow NAT2 alleles have an intermediate acetylator phenotype, and individuals who lack slow NAT2 alleles have a rapid acetylator phenotype.

Molecular mechanisms of NAT2 slow acetylation

The molecular mechanisms responsible for the production of the NAT2 slow acetylator phenotype are not well understood. Initial studies in liver tissue showed that the slow phenotype was due to a marked decrease in NAT2 protein content. In bacterial[4] and yeast[5] expression systems, some base changes caused slow acetylation by producing an unstable protein, whereas others caused slow acetylation by a reduction in NAT2 protein expression.

NAT2 allele frequency

In Caucasian and African populations, the frequency of the slow acetylation phenotype varies between 40% and 70%, whereas that of Asian populations, such as Japanese, Chinese, Korean, and Thai, range from 10% to 30%.[6] This difference reflects slow acetylator allele frequency. Caucasian and African populations have high frequencies of NAT2*5 alleles (>28%) and low frequencies of NAT2*7 alleles (<5%), whereas Asian populations have low incidences of NAT2*5 alleles (<7%) and higher incidences of NAT2*7 alleles (>10%). Also, NAT2*14 alleles are almost absent from Caucasian and Asian populations (< 1%), but are present in African populations at comparably higher frequencies (>8%).

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook

Post a comment