CYP2D6 allele distribution in Macedonians, Albanians and Romanies in the Republic of Macedonia
, , , , and | Jul 09, 2016
About this article
Article Category: Original Article
Published Online: Jul 09, 2016
Page range: 49 - 58
DOI: https://doi.org/10.1515/bjmg-2015-0086
Keywords
© 2016 Walter de Gruyter GmbH, Berlin/Boston
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CYP2D6 allele frequency in Macedonians, Albanians and Romanies.
| Allele and SNP | Location | Amino Acid Change | dbSNP ID | Functional Effect | Allele Frequency | ||
|---|---|---|---|---|---|---|---|
| Macedonians | Albanians | Romanies | |||||
| – | – | – | normal | 0.365 | 0.370 | 0.330 | |
| exon 2 exon 6 | Arg296Cys Ser486Thr | rs16947 rs1135840 | normal | 0.255 | 0.215 | 0.255 | |
| exon 5 | frameshift | rs35742686 | none | 0.020 | 0.035 | 0.015 | |
| intron 3 - exon 4 junction | splicing defect | rs3892097 | none | 0.170 | 0.225 | 0.150 | |
| ‒ | gene deletion | ‒ | none | 0.015 | 0.025 | 0.005 | |
| ‒ | frameshift | rs5030655 | none | 0.010 | 0.015 | 0.005 | |
| ‒ | Lys281del | rs5030656 | decreased | 0.000 | 0.005 | 0.005 | |
| exon 1 | Pro34Ser | rs1065852 | decreased | 0.015 | 0.005 | 0.000 | |
| exon 2 | Thr107Ile | rs28371706 | decreased | 0.000 | 0.000 | 0.000 | |
| ‒ | Arg36His | rs61736512 | decreased | 0.015 | 0.000 | 0.000 | |
| ‒ | Glu242Lys | rs28371725 | decreased | 0.110 | 0.105 | 0.230 | |
| ‒ | gene duplication | ‒ | increased | 0.020 | 0.000 | 0.005 | |
| ‒ | gene duplication | ‒ | increased | 0.005 | 0.005 | 0.000 | |
Genotype frequency of determined CYP2D6 genotypes and corresponding phenotypes.
| Predicted | Genotype | Frequency in Macedonians (%) | Frequency in Albanians (%) | Frequency in Romanies (%) |
|---|---|---|---|---|
| 0.01 | 0.00 | 0.00 | ||
| 0.03 | 0.00 | 0.01 | ||
| 0.01 | 0.01 | 0.00 | ||
| 0.14 | 0.15 | 0.13 | ||
| 0.20 | 0.13 | 0.17 | ||
| 0.00 | 0.00 | 0.01 | ||
| 0.02 | 0.00 | 0.00 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.05 | 0.08 | 0.12 | ||
| 0.06 | 0.05 | 0.07 | ||
| 0.01 | 0.02 | 0.00 | ||
| 0.05 | 0.03 | 0.17 | ||
| 0.01 | 0.03 | 0.01 | ||
| 0.13 | 0.17 | 0.07 | ||
| 0.02 | 0.02 | 0.01 | ||
| 0.00 | 0.02 | 0.01 | ||
| 0.09 | 0.12 | 0.02 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.00 | 0.01 | 0.00 | ||
| 0.03 | 0.02 | 0.03 | ||
| 0.00 | 0.01 | 0.00 | ||
| 0.04 | 0.04 | 0.09 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.00 | 0.01 | 0.02 | ||
| 0.00 | 0.01 | 0.00 | ||
| 0.01 | 0.00 | 0.00 | ||
| 0.00 | 0.01 | 0.00 | ||
| 0.00 | 0.03 | 0.00 | ||
| 0.03 | 0.03 | 0.06 |
Comparison of CYP2D6allele frequencies in different populations.
| Population | Refs | Functional | Non Functional | Reduced | Duplications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | |
| 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 | |
| 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 | |
| 32 | 36.40 | 32.40 | 2.00 | 20.70 | 2.00 | 0.90 | 1.80 | 1.50 | ‒ | ‒ | ‒ | 0.50 | 1.30 | |
| 29 | 76.50 | ‒ | 2.75 | 14.00 | 1.00 | 1.50 | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | 4.00 | |
| 30 | ‒ | ‒ | 2.30 | 17.84 | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | ‒ | 6.01 | |
| 31 | ‒ | ‒ | 1.12 | 22.87 | 3.14 | 0.02 | ‒ | ‒ | ‒ | ‒ | ‒ | 3.14 | ‒ | |
| 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 | |
| 27 | 24.90 | 10.80 | 0.80 | 18.70 | 9.10 | 0.00 | 1.60 | 2.70 | ‒ | ‒ | 8.60 | 5.90 The article does not clearly explain on which alleles the duplications occur. | ||
This study. | ‒ | 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 |
This study. | ‒ | 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 |
This study. | ‒ | 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 |
CYP2D64 major phenotype classes and two subclasses [4,7]The phenotypes were derived from the Human Cytochrome P450 (CYP) Allele Nomenclature Committee website [4] and the PharmGKB website for the related Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2D6 [7]..
| Predicted Drug Metabolizing Phenotype UM: ultrarapid metabolizer; EM: extensive metabolizer; IM: intermediate metabolizer; PM: poor metabolizer. | Combination of Alleles |
|---|---|
| A combination of one normal activity allele with one increased activity allele | |
| Two normal activity alleles; a combination of one increased activity allele with one decreased activity allele | |
| A combination of one normal activity allele with one decreased activity allele; a combination of one increased activity allele with one null activity allele | |
| One normal activity allele with one null activity allele; two decreased activity alleles | |
| A combination of one decreased activity allele with one null activity allele | |
| Only null activity alleles detected |