Table 5.

ITPA Variants and ITPase Deficiency Are Associated With a Reduction in the Week 4 Hb Level: Multivariate Linear Regression Modeling of Week 4 Anemia (Absolute Reduction in Hb)

ITPA Variant	Estimate	Standard Error	P Value
rs1127354	−1.02	0.24	4.73 × 10−5
rs7270101	−0.96	0.19	1.05 × 10−6
ITPA Variant	Adjusted Estimate*	Standard Error	Adjusted P Value*
rs1127354	−1.10	0.23	2.90 × 10−6
rs7270101	−1.01	0.18	6.78 × 10−8
ITPase Deficiency Variable	Estimate	Standard Error	P Value
Grade 0/1/2/3†	−0.75	0.11	3.82 × 10−11

ITPA variants were strongly and independently associated with protection from quantitative Hb reduction during week 4 of therapy. The composite ITPase deficiency variable was more strongly associated with protection from a week 4 quantitative Hb reduction than either individual ITPA variant (the complete multivariate linear regression model, showing estimates for all included variables, is shown in Supporting Information Table 1). The covariates were age, sex, body mass index, baseline Hb level, baseline glomerular filtration rate, METAVIR F3-F4 versus F0–F2, and RBV starting dose (mg/kg). The HCV RNA level, HCV genotype, and sex were not significantly associated with Hb reduction in univariate analyses.

^*Adjusted estimates and P values were calculated with models in which the other functional variant was already included.

^†The ITPase deficiency was graded as follows: 0 = normal activity, 1 = mild deficiency, 2 = moderate deficiency, and 3 = severe deficiency.