Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population.
BACKGROUND
Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 *3, *4 and *14 variants associated with the loss of enzyme function; CYP2D6 *10 and *17 variants with reduced enzyme function; and CYP2D6 *2 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs.


OBJECTIVE
The objective of this study was to determine the prevalence of CYP2D6 *2, *3, *4, *10, *14 and *17 variants in the main ethnic groups in the Sri Lankan population.


METHODS
A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods.


RESULTS
The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 *2: 37%, 41.6% and 37.9%; CYP2D6 *3: 60.3%, 45% and 30%; CYP2D6 *4: 21.6%, 6.6% and 8.3%; CYP2D6 *10: 40%, 35% and 44%. CYP2D6 *14 and *17 variants were not identified.


CONCLUSIONS
CYP2D6*3, *4 and *10 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6*4, which is reported to be a Caucasian variant was also found in all three ethnic groups.
Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
T D Praveen
TD
Tharanga
Department of Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
C M V
CM
Jinadasa
Department of Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
M F
MF
Risama
Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
Priyadarshani
P
Galappatthy
Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
R L
RL
Jayakody
Department of Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka.
Vajira H W
VH
Dissanayake
Allele frequency; Sri Lankan; cytochrome P450 2D6