Haplotypic analysis of the VKORC1 gene among the 222 healthy volunteers in relation to AC response
VKORC1 SNPs . | . | . | . | . | . | . | Phenotypic change, % (95% CI) . | . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| -4931T>C . | -4451C>A . | -2659G>C . | -1639G>A . | 497T>G . | 1173C>T . | Frequency . | Factor VII ratio . | INR change . | |||||||
| C | C | G | A | G | T | 0.27 | 19 (17-21) | 18 (16-20) | |||||||
| C | C | G | A | T | T | 0.12 | 19 (14-23) | 19 (16-22) | |||||||
| T | C | G | A | G | T | 0.019 | 19 (8-31) | 16 (4-28) | |||||||
| T | C | G | G | T | C | 0.23 | 34 (32-37) | 7 (4-10) | |||||||
| T | A | C | G | T | C | 0.21 | 37 (34-40) | 4 (-0.7-8) | |||||||
| T | A | G | G | T | C | 0.11 | 38 (33-42) | 3 (-2-9) | |||||||
| C | C | G | G | T | C | 0.017 | 42 (22-61) | -2 (-18-14) | |||||||
VKORC1 SNPs . | . | . | . | . | . | . | Phenotypic change, % (95% CI) . | . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| -4931T>C . | -4451C>A . | -2659G>C . | -1639G>A . | 497T>G . | 1173C>T . | Frequency . | Factor VII ratio . | INR change . | |||||||
| C | C | G | A | G | T | 0.27 | 19 (17-21) | 18 (16-20) | |||||||
| C | C | G | A | T | T | 0.12 | 19 (14-23) | 19 (16-22) | |||||||
| T | C | G | A | G | T | 0.019 | 19 (8-31) | 16 (4-28) | |||||||
| T | C | G | G | T | C | 0.23 | 34 (32-37) | 7 (4-10) | |||||||
| T | A | C | G | T | C | 0.21 | 37 (34-40) | 4 (-0.7-8) | |||||||
| T | A | G | G | T | C | 0.11 | 38 (33-42) | 3 (-2-9) | |||||||
| C | C | G | G | T | C | 0.017 | 42 (22-61) | -2 (-18-14) | |||||||
Construction and estimated frequencies of haplotypes were provided by the new THESIAS software (http://ecgene.net/genecanvas/modules/mydownloads/singlefile.php?cid=1&lid=4).
Phenotypic changes are expressed as the percentage, compared with baseline values, before AC intake, of factor VII ratio or INR change resulting from the one-dose effect of haplotype (each individual carrying 2 haplotypes).
Factor VII ratio corresponds to remaining factor VII, expressed as a percentage compared with baseline value, before AC intake (eg, [Factor VII 24 h after AC intake/Factor VII before AC intake] × 100).
INR change is expressed as the formula: (INR 24 h after AC intake — INR before AC intake/INR before AC intake) × 100.
The low frequency of SNP -1877A>G does not permit the study of the effect on AC response of the corresponding haplotype (frequency = 0.007).
Negative values for phenotypic change in the INR change column reflect the low variation among this haplotype.
Likelihood ratio test was used for a global haplotypic effect: χ2 = 95.43 with 6 df, p < 10-4.