TABLE 2.
Variants in DPYD are associated with altered UH2/ dihydrouracil/uracil ratios
| Allele frequencies | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Genetic variant | P‐valuea | Log2 βa | % change in ratiosa | Combined cohortb | Sistonen et al.20 | Hamzic et al. | Meulendijks et al.21 | Nie et al.22, c | dbSNPd (EUR) |
| c.1129‐5923C > G (rs75017182) | .0003 | −0.20 | −13.2% | 3.66% | 1.56% | 2.11% | 2.00% | 13.72% | 2.39% |
| c.1679T > G (rs55886062) | 9.2 × 10 −7 | −0.89 | −46.0% | 0.29% | 0.32% | 0.32% | 0.18% | 0.49% | 0.06% |
| c.1905 + 1G > A (rs3918290) | 1.5 × 10 −9 | −0.83 | −43.7% | 0.54% | 0.16% | 0.16% | 0b | 3.18% | 0.50% |
| c.2846A > T (rs67376798) | 8.0 × 10 −10 | −0.67 | −37.1% | 0.83% | 0.31% | 0.48% | 0.54% | 2.90% | 0.42% |
| c.85T > C (rs1801265) | .067 | +0.06 | +2.4% | 24.63%b | 22.50% | 23.00% | NAb | 30.10% | 21.79% |
| c.496A > G (rs2297595) | 8.7 × 10 −6 | −0.20 | −12.6% | 10.81%b | 12.50% | 11.50% | NAb | 7.10% | 11.93% |
P‐values and β‐coefficients were calculated in the complete cohort using a multivariate model with sex, study cohort, and DPYD risk variants as independent variables; P‐values < .01 are in bold, and % change in ratios is given per allele. DPYD risk variants have been included in the same linear mixed model using an ANOVA‐based approach (P anova = 2 × 10−16). For c.85T > C and c.496A > G, individual linear mixed models were performed including DPYD risk status as a co‐factor.
The study from Meulendijks et al.21 excluded carriers of c.1905 + 1G > A in their study and was not genotyped for c.85T > C and c.496A > G; the complete study population size for c.85T > C and c.496A > G is n = 832.
The cohort of Nie et al.22 was enriched for DPYD risk variant carriers (c.1129‐5923C > G,c.1679T > G, c.1905 + 1G > A, and c.2846A > T).
European population (EUR), https://www.ncbi.nlm.nih.gov/snp.