Table 1
| Predicted Drug Metabolizing Phenotypeb | Combination of Alleles |
|---|---|
| UM | A combination of one normal activity allele with one increased activity allele |
| EM | Two normal activity alleles; a combination of one increased activity allele with one decreased activity allele |
| IM to EM | A combination of one normal activity allele with one decreased activity allele; a combination of one increased activity allele with one null activity allele |
| IM | One normal activity allele with one null activity allele; two decreased activity alleles |
| PM to IM | A combination of one decreased activity allele with one null activity allele |
| PM | Only null activity alleles detected |
Representative electropherogram of homozygous patient with genotype *4/*4.
A) Representative electropherogram of a heterozygous patient without a duplication. B) Representative electropherogram of a heterozygous patient with a duplication.
Table 2
CYP2D6 allele frequency in Macedonians, Albanians and Romanies.
| Allele and SNP | Location | Amino Acid Change | dbSNP ID | Functional Effect | Allele Frequency | ||
|---|---|---|---|---|---|---|---|
| Macedonians | Albanians | Romanies | |||||
| *1: wild type | – | – | – | normal | 0.365 | 0.370 | 0.330 |
| *2: 2850(C>T) 4180 (G>C) | exon 2 exon 6 | Arg296Cys Ser486Thr | rs16947 rs1135840 | normal | 0.255 | 0.215 | 0.255 |
| *3: 2549delA | exon 5 | frameshift | rs35742686 | none | 0.020 | 0.035 | 0.015 |
| *4: 1846 (G>A) | intron 3 - exon 4 junction | splicing defect | rs3892097 | none | 0.170 | 0.225 | 0.150 |
| *5 | ‒ | gene deletion | ‒ | none | 0.015 | 0.025 | 0.005 |
| *6: 1707delT | ‒ | frameshift | rs5030655 | none | 0.010 | 0.015 | 0.005 |
| *9: 2615-2617delAAG | ‒ | Lys281del | rs5030656 | decreased | 0.000 | 0.005 | 0.005 |
| *10: 100 (C>T) | exon 1 | Pro34Ser | rs1065852 | decreased | 0.015 | 0.005 | 0.000 |
| *17: 1023 (C>T) | exon 2 | Thr107Ile | rs28371706 | decreased | 0.000 | 0.000 | 0.000 |
| *29: 1661 (G>C) | ‒ | Arg36His | rs61736512 | decreased | 0.015 | 0.000 | 0.000 |
| *41: 2988 (G>A) | ‒ | Glu242Lys | rs28371725 | decreased | 0.110 | 0.105 | 0.230 |
| *1xN | ‒ | gene duplication | ‒ | increased | 0.020 | 0.000 | 0.005 |
| *2xN | ‒ | gene duplication | ‒ | increased | 0.005 | 0.005 | 0.000 |
SNP: single nucleotide polymorphism; dbSNP: database SNP.
Table 3
Genotype frequency of determined CYP2D6 genotypes and corresponding phenotypes.
| Predicted | Genotype | Frequency in Macedonians (%) | Frequency in Albanians (%) | Frequency in Romanies (%) |
|---|---|---|---|---|
| Ultrarapid metabolizer | *1xN/*1 | 0.01 | 0.00 | 0.00 |
| *1xN/*2 | 0.03 | 0.00 | 0.01 | |
| *2xN/*2 | 0.01 | 0.01 | 0.00 | |
| Extensive metabolizer | *1/*1 | 0.14 | 0.15 | 0.13 |
| *1/*2 | 0.20 | 0.13 | 0.17 | |
| *1/*9 | 0.00 | 0.00 | 0.01 | |
| *1/*10 | 0.02 | 0.00 | 0.00 | |
| *1/*29 | 0.01 | 0.00 | 0.00 | |
| *2/*29 | 0.01 | 0.00 | 0.00 | |
| *1/*41 | 0.05 | 0.08 | 0.12 | |
| *2/*2 | 0.06 | 0.05 | 0.07 | |
| *2/*3 | 0.01 | 0.02 | 0.00 | |
| *2/*41 | 0.05 | 0.03 | 0.17 | |
| Intermediate metabolizer | *1/*3 | 0.01 | 0.03 | 0.01 |
| *1/*4 | 0.13 | 0.17 | 0.07 | |
| *1/*5 | 0.02 | 0.02 | 0.01 | |
| *1/*6 | 0.00 | 0.02 | 0.01 | |
| *2/*4 | 0.09 | 0.12 | 0.02 | |
| *2/*5 | 0.01 | 0.00 | 0.00 | |
| *2/*6 | 0.00 | 0.01 | 0.00 | |
| *41/*41 | 0.03 | 0.02 | 0.03 | |
| *9/*41 | 0.00 | 0.01 | 0.00 | |
| *4/*41 | 0.04 | 0.04 | 0.09 | |
| *4/*29 | 0.01 | 0.00 | 0.00 | |
| *6/*10 | 0.01 | 0.00 | 0.00 | |
| *6/*41 | 0.01 | 0.00 | 0.00 | |
| *3/*41 | 0.00 | 0.01 | 0.02 | |
| *4/*10 | 0.00 | 0.01 | 0.00 | |
| Poor metabolizer | *3/*3 | 0.01 | 0.00 | 0.00 |
| *3/*4 | 0.00 | 0.01 | 0.00 | |
| *4/*5 | 0.00 | 0.03 | 0.00 | |
| *4/*4 | 0.03 | 0.03 | 0.06 |
Table 4
Comparison of CYP2D6allele frequencies in different populations.
| Population | Refs | Functional | Non Functional | Reduced | Duplications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| *1 | *2 | *3 | *4 | *5 | *6 | *9 | *10 | *17 | *29 | *41 | *1xN | *2xN | ||
| French | 15 | 28.00 | 32.00 | 0.00 | 16.00 | 4.00 | 0.00 | 4.00 | 2.00 | 0.00 | 0.00 | 10.00 | 2.00 | 0.00 |
| Sardinian | 15 | 28.60 | 35.70 | 1.80 | 21.40 | 1.80 | 0.00 | 0.00 | 5.40 | 0.00 | 0.00 | 3.60 | 0.00 | 1.80 |
| Russian | 15 | 32.00 | 34.00 | 0.00 | 20.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 8.00 | 0.00 | 4.00 |
| German | 32 | 36.40 | 32.40 | 2.00 | 20.70 | 2.00 | 0.90 | 1.80 | 1.50 | ‒ | ‒ | ‒ | 0.50 | 1.30 |
| Croatian | 29 | 76.50 | ‒ | 2.75 | 14.00 | 1.00 | 1.50 | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | 4.00 |
| Greek | 30 | ‒ | ‒ | 2.30 | 17.84 | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | 6.01 |
| Czech | 31 | ‒ | ‒ | 1.12 | 22.87 | 3.14 | 0.02 | ‒ | ‒ | ‒ | ‒ | ‒ | 3.14 | ‒ |
| Bedouin | 15 | 35.70 | 20.40 | 0.00 | 5.10 | 4.10 | 2.00 | 0.00 | 0.00 | 3.10 | 0.00 | 22.40 | 1.00 | 2.00 |
| Macedonian | 27 | 24.90 | 10.80 | 0.80 | 18.70 | 9.10 | 0.00 | 1.60 | 2.70 | ‒ | ‒ | 8.60 | 5.90a | |
| Macedonianb | ‒ | 36.50 | 25.50 | 2.00 | 17.00 | 1.50 | 1.00 | 0.00 | 1.50 | 0.00 | 1.50 | 11.00 | 2.00 | 0.50 |
| Albanianb | ‒ | 37.00 | 21.50 | 3.50 | 22.50 | 2.50 | 1.50 | 0.50 | 0.50 | 0.00 | 0.00 | 10.50 | 0.00 | 0.50 |
| Romanyb | ‒ | 33.00 | 25.40 | 1.50 | 15.00 | 0.50 | 0.50 | 0.50 | 0.00 | 0.00 | 0.00 | 23.00 | 0.50 | 0.00 |
The calculated percentage of metabolizing classes within the Macedonian, Albanian and Romany population (EM: extensive metabolizers; IM: intermediate metabolizers; PM: poor metabolizers; UM: ultrarapid metabolizers).