TY - JOUR
T1 - Genetic polymorphisms in warfarin and tacrolimus-related genes VKORC1, CYP2C9 and CYP3A5 in the Greek-Cypriot population
AU - Hadjipanagi, Despina
AU - Chrysanthou, Stephanie
AU - Voskarides, Konstantinos
AU - Deltas, Constantinos
PY - 2014/3/5
Y1 - 2014/3/5
N2 - Background: Two variants in the gene encoding the cytochrome P450 2C9 enzyme (CYP2C9) are considered the most significant genetic risk factors associated with bleeding after warfarin prescription. A variant in the vitamin K epoxide reductase (VKORC1) has been also associated by several studies with warfarin response. Another variant in the P450 3A5 enzyme (CYP3A5) gene is known to affect the metabolism of many drugs, including tacrolimus. Findings. We conducted a population genetic study in 148 unrelated healthy Greek-Cypriot volunteers (through PCR-RFLP assays), in order to determine the frequencies of the above pharmacogenetics variants and to compare allele frequencies with those in other major ethnic groups. The allele frequencies of CYP2C9*2, CYP2C9*3 and CYP3A5*3 were found to be 0.162, 0.112 and 0.943 respectively, whereas VKORC1 - 1639A was 0.534. The latter frequency differs significantly when compared with Caucasians, Asians and Africans (p < 0.001) and is still significant when compared with the geographically and culturally closely related to Greek-Cypriots, Hellenes of Greece (p = 0.01). Interestingly ∼18% of our population are carriers of four or three risk alleles regarding warfarin sensitivity, therefore they have a high predisposition for bleeding after taking high or even normal warfarin doses. Conclusions: Our data show no significant difference in the frequency of CYP2C9 and CYP3A5 allelic variants when compared to the Caucasian population, but differ significantly when compared with Africans and Asians (p < 0.001). Also, the frequency of variant VKORC1 - 1639A differs between Greek-Cypriots and every other population we compared. Finally, about 1/5 Greek-Cypriots carry three or four risk alleles and ∼50% of them carry at least two independent risk alleles regarding warfarin sensitivity, a potentially high risk for over-anticoagulation.
AB - Background: Two variants in the gene encoding the cytochrome P450 2C9 enzyme (CYP2C9) are considered the most significant genetic risk factors associated with bleeding after warfarin prescription. A variant in the vitamin K epoxide reductase (VKORC1) has been also associated by several studies with warfarin response. Another variant in the P450 3A5 enzyme (CYP3A5) gene is known to affect the metabolism of many drugs, including tacrolimus. Findings. We conducted a population genetic study in 148 unrelated healthy Greek-Cypriot volunteers (through PCR-RFLP assays), in order to determine the frequencies of the above pharmacogenetics variants and to compare allele frequencies with those in other major ethnic groups. The allele frequencies of CYP2C9*2, CYP2C9*3 and CYP3A5*3 were found to be 0.162, 0.112 and 0.943 respectively, whereas VKORC1 - 1639A was 0.534. The latter frequency differs significantly when compared with Caucasians, Asians and Africans (p < 0.001) and is still significant when compared with the geographically and culturally closely related to Greek-Cypriots, Hellenes of Greece (p = 0.01). Interestingly ∼18% of our population are carriers of four or three risk alleles regarding warfarin sensitivity, therefore they have a high predisposition for bleeding after taking high or even normal warfarin doses. Conclusions: Our data show no significant difference in the frequency of CYP2C9 and CYP3A5 allelic variants when compared to the Caucasian population, but differ significantly when compared with Africans and Asians (p < 0.001). Also, the frequency of variant VKORC1 - 1639A differs between Greek-Cypriots and every other population we compared. Finally, about 1/5 Greek-Cypriots carry three or four risk alleles and ∼50% of them carry at least two independent risk alleles regarding warfarin sensitivity, a potentially high risk for over-anticoagulation.
KW - CYP2C9
KW - CYP3A5
KW - Cyprus
KW - Greek-Cypriots
KW - Pharmacogenetics
KW - Population genetics
KW - VKORC1
UR - http://www.scopus.com/inward/record.url?scp=84898549380&partnerID=8YFLogxK
U2 - 10.1186/1756-0500-7-123
DO - 10.1186/1756-0500-7-123
M3 - Article
C2 - 24593903
AN - SCOPUS:84898549380
SN - 1756-0500
VL - 7
JO - BMC Research Notes
JF - BMC Research Notes
IS - 1
M1 - 123
ER -