CYP2D6 gene test in psychiatric patients and healthy volunteers.
BACKGROUND
Antipsychotic drug therapy meets difficulties in predicting response in psychiatric patients. The medical treatment of these patients may be improved significantly by systematic phamacogenetic diagnosis identifying the drug metabolic capacities of each patient. Genetic polymorphisms in the coding sequence for the drug metabolizing cytochrome P450 enzyme CYP2D6 represent a pharmacogenetic target.


METHODS
A cohort (n = 225) representing psychiatric patients seen during an 18-month trial period was included in the project after the subjects accepted a blood sample being taken to analyse their CYP2D6 allelic composition. To investigate any putative difference in allele frequencies among the psychiatric patients compared to earlier publications on allele frequencies in Caucasian populations, another cohort (n = 122) of local healthy volunteers was likewise included.


RESULTS
Allelic frequencies in the psychiatric patients and healthy volunteers were indistinguishable. Alleles *1 and *2 encoding for normal enzyme activity and alleles *3, *4, *5, *6, *13/*16 representing non-active forms were found as well as alleles *9, *10, *41 encoding for enzymes with decreased activity. Furthermore, examples of the previously described duplications of *1 and *2, which result in enhanced enzyme activity, were also identified.


CONCLUSIONS
A systematic CYP2D6 gene test of hospitalized psychiatric patients revealed the identification of pharmacogenetically relevant alleles affecting capacity to metabolize antipsychotics. The frequencies of phenotypes in affected patients were 8.4 % intermediate metabolizers (IMs), 8.4 % poor metabolizers (PMs) and 3.1 % ultrafast metabolizers (UMs), whereas 52.4 % were extensive metabolizers (EMs) and 27.6 % heterozygous EMs.
Danish Epilepsy Centre, Laboratory, Dianalund, Denmark.
J O
JO
Rasmussen
M
M
Christensen
J M
JM
Svendsen
O
O
Skausig
E L
EL
Hansen
K A
KA
Nielsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000201:enzymology* / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6