View source for Phenotype:UGT1A1 normal metabolizer

A '''UGT1A1 normal metabolizer''' (NM) is a person whose ''UGT1A1'' alleles together produce the typical, reference level of enzyme activity. It is one of the three metabolizer phenotypes assigned from ''UGT1A1'' genotype, above the [[Phenotype:UGT1A1 poor metabolizer|poor metabolizer]] and [[Phenotype:UGT1A1 intermediate metabolizer|intermediate metabolizer]]. UGT1A1 has no rapid or ultrarapid phenotype, so the normal metabolizer is the highest-activity phenotype on the scale. This page describes the normal-metabolizer phenotype; the enzyme itself is covered at [[Enzyme:UGT1A1]].

The normal metabolizer is the reference phenotype. The standard dose of [[Irinotecan|irinotecan]] in chemotherapy regimens is calibrated to normal-metabolizer populations, and for a normal metabolizer UGT1A1 genotype is not a reason to depart from standard dosing.

== Genotype basis ==
The normal-metabolizer phenotype is produced by the ''\*1/\*1'' diplotype: two copies of the reference allele, which carries the A(TA)6TAA promoter (TA6). The full allele catalogue is described on the [[Enzyme:UGT1A1]] page.

== Population frequency ==
The UGT1A1 normal-metabolizer phenotype is found in roughly 40 to 50% of European-ancestry populations, with frequencies elsewhere varying as the reduced-function alleles vary. Because the ''\*28'' allele is common in every population, the normal metabolizer is typically not an overwhelming majority; in many populations the intermediate-metabolizer phenotype is as common or more so.

== Clinical significance ==
For a UGT1A1 normal metabolizer, standard dosing of UGT1A1-affected medicines applies. [[Irinotecan|Irinotecan]] can be given at its standard regimen dose without a genotype-driven reduction, and a normal metabolizer given [[Atazanavir|atazanavir]] is at low risk of the clinically apparent jaundice that affects poor metabolizers.

The normal metabolizer also has a fully normal capacity to conjugate bilirubin and therefore does not have the mild unconjugated hyperbilirubinemia of Gilbert syndrome, which belongs to the poor-metabolizer phenotype.

The standing caveat applies: a normal metabolizer given a UGT1A1 inhibitor, atazanavir being the prime example, has reduced UGT1A1 function for the duration of the exposure, a phenocopy of a lower-activity phenotype. Normal-metabolizer genotype does not prevent that interaction, though the resulting hyperbilirubinemia in a normal metabolizer is milder than in a poor metabolizer.

== See also ==
* [[Enzyme:UGT1A1]], the enzyme, its history, and its full substrate spectrum.
* [[Phenotype:UGT1A1 poor metabolizer]], [[Phenotype:UGT1A1 intermediate metabolizer]], the sibling phenotypes.
* [[Irinotecan]], [[Atazanavir]] (representative affected medicines).
* [[:Category:Pharmacogenomic phenotypes]]

== References ==

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[[Category:Pharmacogenomic phenotypes]]