Page 115 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Supplement
Heterozygous for variants with reduced functionality or inactive functionality (*2A/c.2846A>Tc.2846A>T or *1/*2A+c.2846A>T; *13/c.2846A>Tc.2846A>T or *1/*13+c.2846A>T; *2A/c.1236G>A or *1/*2A+c.1236G>A; *13/c.1236G>A or *1/*13+c.1236G>A)
Heterozygous for two different variants with inactive functionality
(*2A/*13 or *1/*2A+*13)
Homozygous for one variant with reduced functionality and heterozygous for the other variant with reduced functionality
(c.2846A>T/c.2846A>T+ c.1236G>A
or c.1236G>A/c.2846A>T+ c.1236G>A)
Gene activity score 0.5 or 1 (25% or 50% of normal DPD enzyme activity), phenotyping is required to quantify DPD enzyme activity
Gene activity score 0 or 1
(0% or 50% of normal DPD enzyme activity), phenotyping is required to quantify DPD enzyme activity
Gene activity score 0.5 to 1 (25% to 50% of normal DPD enzyme activity), phenotyping is required to quantify DPD enzyme activity
However, other factors than genetic variants
can also affect the DPD enzyme activity.
For this reason, one should resort to the recommendation for the gene activity score
of 1 when the measured DPD enzyme activity
is approximately equal to 50% of normal DPD
enzyme activity and to the recommendation
for the gene activity score of 1.5 when the
measured DPD enzyme activity is approximately
equal to 75% of normal DPD enzyme activity. 4
When the measured DPD enzyme activity is between 50% and 75% (e.g. 63%) one should resort to the recommendation for gene activity score 1. In this case, one should record a gene activity score of 1.25 in the patients’ medical record.
When two variants are located on different alleles the gene activity score is 0.5 (one allele with reduced functionality and one allele with inactive functionality).
When two variants are located on the same allele, the gene activity score is 1 (one allele with full functionality and one allele with inactive functionality).
When two variants are located on different alleles the gene activity score is 0 (two alleles with inactive functionality).
When two variants are located on the same allele the gene activity score is 1 (one allele with full functionality and one allele with inactive functionality).
One of the alleles has an activity of 0.5. The activity of the other allele is unknown, but lies between 0 and 0.5 (see reasoning for heterozygous for two different alleles with reduced functionality).
One should resort to the recommendation for gene activity score 0.5 when the measured
DPD enzyme activity is approximately 25%
of normal DPD enzyme activity and to the recommendation of gene activity score 1 when the DPD enzyme activity is 50% of normal DPD enzyme activity.
When the measured DPD enzyme activity is between 25% and 50% (e.g. 38%) one should resort to the recommendation for gene activity score 0.5. In this case, one should record a gene activity score of 0.75 in the patients’ medical record.
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