INVESTIGADORES
BUZALEH Ana Maria
congresos y reuniones científicas
Título:
Polymorphisms of CYP2D6 in control and porphyric individuals.
Autor/es:
LAVANDERA, JIMENA; MC KEON, SOLEDAD; PARERA, VICTORIA; ROSSETTI, MARIA VICTORIA; BATLLE, ALCIRA; BUZALEH, ANA MARIA
Lugar:
Estocolmo
Reunión:
Congreso; PORPHYRINS AND PORPHYRIAS 2009; 2009
Institución organizadora:
Swedish Society of Medicine
Resumen:
CYP2D6 polymorphisms result in poor (PM), intermediate
(IM), ultrarapid (UM), efficient (EM) and
efficient intermediate metabolizers (EIM). Nowadays,
it is known that CYP2D6 polymorphisms cause
inter-individual variability in drug response influencing
the treatment of several diseases.
Some of CYP2D6 substrate drugs are unsafe for porphyric
patients, so, polymorphisms in these individuals
could influence in the triggering of the disease
when they receive a precipitating agent metabolized
by this isoform.
Previously we investigated the presence of PM in individuals
with different types of Porphyria; a lower
PM frequency in porphyric patients respect to control
group was observed.
The aim of this work was to identify CYP2D6 UM
frecuency in porphyric patients and in a control
group.
A total of 87 subjects, 46 healthy volunteers and 41
porphyric patients: 22 with Acute Intermittent Porphyria
(AIP) and 19 with Porphyria Cutanea Tarda
(PCT) were included in the study. To identify individuals
carrying duplicate CYP2D6 genes, long-range
PCR was used according to Steijns & Der Weide
(Clin. Chem. 44:5, 1998, 914917) with slight modifications.
PCR-RFLP.was also performed to identify
CYP2D6*4 allele to avoid misclassification of subjects
with *4xN nonfunctional duplication.
Genotype distribution of CYP2D6 alleles showed
that 13% (6/46) of control group have CYP2D6 duplicated;
none of these individuals presented CYP2D6*4
allele. In PCT group, 5.3% (1/19) had the CYP2D6
gene duplicated. In AIP group, 4.5% (1/22) of patients
showed duplicated CYP2D6 alleles. Predicted
phenotype distribution reveals that 50% of control
group were classified as EM, 35% as EIM, 2.2% as
PM and 13% as UM. In AIP group, 86.4% were EM,
9.1% EIM, being these results significantly different
respect to control group (p<0.01) and 4.5% as UM. In
PCT 63.2% were classified as EM, 26.3% as EIM, 5.3%
as PM and UM.
The information obtained with this research would
be of impact on the practice of medicine in a near
future. Some drugs have shown conflictive evidence
about their porphyrinogenicity in some individuals.
So, predictive genotyping for CYP2D6 in porphyric
patients could be used soon routinarily to improve
the clinical efficacy of drug therapy and to personalize
drug administration.