Table 2. Observed frequencies of DME gene variants.
|
Genotype frequency |
Minor allele frequency |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Allele | Variant | rs number | Function | Genotypes | Sing (n=164) | Leb (n=78) | POSH (n=345) | Total (n=587) | Sing | Leb | POSH | Total |
| CYP2D6 | ||||||||||||
| *3 | 2549delA | rs35742686 | Abrogated | A/A | 1.00 | 1.00 | 0.97 | 0.98 | 0 | 0 | 0.02† | 0.01 |
| A/del | 0 | 0 | 0.03 | 0.02 | ||||||||
| del/del | 0 | 0 | 0.003 | 0.002 | ||||||||
| *4 | g1846 G>A | rs3892097 | Abrogated | G/G | 0.99 | 0.76 | 0.63 | 0.75 | 0.003 | 0.141 | 0.21 | 0.15 |
| G/A | 0.01 | 0.21 | 0.31 | 0.21 | ||||||||
| A/A | 0 | 0.04 | 0.06 | 0.04 | ||||||||
| *5 | Chromosomal deletion | Abrogated | wt/wt | 0.87 | 0.94 | 0.93 | 0.91 | 0.067 | 0.032 | 0.035 | 0.04 | |
| wt/del | 0.13 | 0.06 | 0.07 | 0.09 | ||||||||
| del/del | 0 | 0 | 0 | 0 | ||||||||
| *6 | 1707delT | rs5030655 | Abrogated | T/T | 1.00 | 0.97 | 0.97 | 0.98 | 0 | 0.013 | 0.02 | 0.01 |
| T/del | 0.00 | 0.03 | 0.03 | 0.02 | ||||||||
| del/del | 0 | 0 | 0 | 0 | ||||||||
| *9 | 2615_2617delAAG | rs5030656 | Reduced | AAG/AAG | 1.00 | 1.00 | 0.94 | 0.97 | 0 | 0 | 0.03† | 0.02 |
| AAG/del | 0 | 0 | 0.05 | 0.03 | ||||||||
| del/del | 0 | 0 | 0.01 | 0.003 | ||||||||
| *10 | g100 C>T | rs1065852 | Reduced | C/C | 0.31 | 0.99 | 0.97 | 0.79 | 0.488π | 0.006 | 0.02 | 0.15 |
| C/T | 0.40 | 0.01 | 0.03 | 0.13 | ||||||||
| T/T | 0.29 | 0 | 0 | 0.08 | ||||||||
| *41 | g2988 G>A | rs28371725 | Reduced | G/G | 0.93 | 0.72 | 0.79 | 0.82 | 0.037 | 0.154 | 0.11 | 0.1 |
| G/A | 0.06 | 0.26 | 0.19 | 0.16 | ||||||||
| A/A | 0.01 | 0.03 | 0.01 | 0.01 | ||||||||
| *XN | Duplication | Increased | 2 copies | 0.99 | 0.87 | 0.99 | 0.98 | 0.007‡ | 0.128‡ | 0.003‡ | 0.02‡ | |
| >2 copies | 0.01 | 0.13 | 0.002 | 0.02 | ||||||||
| CYP2C19 | ||||||||||||
| *2 | 681 G>A | rs4244285 | Abrogated | G/G | 0.48 | 0.79 | 0.75 | 0.67 | 0.326 | 0.116 | 0.145 | 0.19 |
| G/A | 0.40 | 0.18 | 0.23 | 0.27 | ||||||||
| A/A | 0.13 | 0.03 | 0.02 | 0.05 | ||||||||
| *3 | 636 G>A | rs4986893 | Abrogated | G/G | 0.90 | 0.90 | 0.052 | nd | nd | 0.05 | ||
| G/A | 0.09 | 0.09 | ||||||||||
| A/A | 0.01 | 0.01 | ||||||||||
| *17 | −806 C>T | rs12248560 | Increased | C/C | 0.92 | 0.62 | 0.67 | 0.74 | 0.04 | 0.216 | 0.2# | 0.15 |
| C/T | 0.08 | 0.32 | 0.26 | 0.22 | ||||||||
| T/T | 0.00 | 0.05 | 0.07 | 0.04 | ||||||||
| CYP2C9 | ||||||||||||
| *2 | c430 C>T | rs1799853 | Reduced | C/C | 1.00 | 0.83 | 0.75 | 0.83 | 0 | 0.087 | 0.14 | 0.09 |
| C/T | 0.00 | 0.17 | 0.23 | 0.15 | ||||||||
| T/T | 0.00 | 0.00 | 0.02 | 0.01 | ||||||||
| *3 | c1075 A>C | rs1057910 | Reduced | A/A | 0.91 | 0.88 | 0.85 | 0.87 | 0.046 | 0.06 | 0.08 | 0.07 |
| A/C | 0.08 | 0.12 | 0.14 | 0.13 | ||||||||
| C/C | 0.01 | 0.00 | 0.003 | 0.002 | ||||||||
| CYP3A5 | ||||||||||||
| *3 | 6986 A>G | rs776746 | Markedly reduced | A/A | 0.10 | 0.01 | 0.02 | 0.05 | 0.72 | 0.91 | 0.91Φ | 0.85 |
| A/G | 0.36 | 0.15 | 0.14 | 0.21 | ||||||||
| G/G | 0.54 | 0.83 | 0.84 | 0.75 | ||||||||
Abbreviations: c, cDNA; del, deletion; DME, drug-metabolizing enzymes; g, gDNA; Leb, Lebanon; nd, not determined; POSH, Prospective study of Outcomes in Sporadic versus Hereditary breast cancer; Sing, Singapore; w, wildtype; wt, wildtype referring to major, that is, functional alleles.
Note-Nucleotide positions refer to numbering according to the ATG start codon. CYP2D6*14, *15 and *17 alleles were detected by AmpliChip quality control only and were not included in the table.
*XN, refers to duplication of EM alleles resulting in UM phenotype.
‡Refers to prevalence of UM phenotype based on multiple copies of functional alleles.
Genotype frequencies that deviate from HWE have the following P values: †P=0.02; πP=0.045; #P=0.006; ΦP=0.003.