Role of genetic polymorphisms in hepatitis C virus chronic infection

Table 2 Studies on the role of inosine triphosphate pyrophosphatase polymorphisms in hepatitis C virus chronic infection

Ref.	No. ofpatients	Country	Type of study	SNPs	Liver disease/HCV genotype	Therapy	Outcome
Thompson et al[30]	304	United States	Retrospective	rs1127354 rs7270101	CHC/1	Peg-IFN-α-2a + RBV	Hb reduction > 3 g/dL at week 4 ITPase deficiency (both SNPs): OR = 0.26, 95%CI: 0.15-0.4; P = 2.7 × 10-7
Eskesen et al[128]	457	Norway	Retrospective	rs1127354 rs7270101	CHC/2/3	Peg-IFN-α-2b + RBV	Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced: OR = 0.39, 95%CI: 0.16-0.96, P = 0.040
Seto et al[129]	60	Hong Kong	Prospective	rs1127354	CHC/6	Peg-IFN + RBV	ITPA rs1127354 CA vs CC genotype: lesser degree of anemia throughout therapy P < 0.05 for all time points
Hai et al[122]	66	Japan	Retrospective	rs1127354	CHC/1	Peg-IFN + RBV	At multiple regression analysis, age < 60 yr, ITPA CA/AA genotype and serum RBV concentration were significant independent predictive factors for SVR
Thompson et al[116]	238	United States	Retrospective	rs1127354 rs7270101	CHC/2/3	PegIFN-α-2b + RBV	Hb reduction at week 4 ITPase deficiency (both SNPs): P = 10(-11) There was no association between the ITPA variants and SVR
Ahmed et al[123]	102	Egypt	Prospective	rs1127354	CHC 1/4	Peg-IFN + RBV	CC patients had more frequently Hb decline > 3 g/dL than non-CC patients at weeks 8 and 12 (P = 0.024 and 0.038, respectively) Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P = 0.021)
Azakami et al[124]	830	Japan	Retrospective	rs1127354	CHC/1	Peg-IFN + RBV	Cumulative reduction of ribavirin was significantly more frequent in genotype CC patients than non-CC patients (OR = 1.928, P = 8.6 × 10-8)
Kurosaki et al[125]	446	Japan	Prospective	rs1127354	CHC/1	Peg-IFN + RBV	ITPA AA/CA had the lowest incidence of anemia (17%)
Matsuura et al[126]	309	Japan	Retrospective	rs1127354	CHC/1	Peg-IFN + RBV	The incidence of severe anemia, ≥ 3 g/dL reduction or < 10 g/dL of Hb up to week 12 was more frequent in patients with CC (65% and 33%) than in those with CA/AA (25%, 6%); P < 0.0001)
Rau et al[130]	216	Switzerland	Retrospective	rs1127354 rs7270101	CHC Mixed genotype	Peg-IFN + RBV	ITPA SNP rs1127354 was associated with Hb drop ≥ 3 g/dL during treatment (RR = 2.1, 95%CI: 1.3-3.5)
Clark et al[131]	193	Australia	Retrospective	rs1127354 rs7270101	CHC Mixed genotype	Peg-IFN + RBV	More severe ITPA deficiency was associated with a lesser reduction in Hb level (P < 0.001), lesser ribavirin dose reduction (P = 0.005), lesser EPO use (P = 0.029) ITPA deficiency was associated with SVR (P = 0.041)
Rembeck et al[132]	354	Sweden	Prospective	rs1127354 rs7270101	CHC/2/3	Peg-IFN + RBV	Reduced ITPase activity was associated with a decreased risk of anemia (P < 0.0001), increased risk of thrombocytopenia (P = 0.007), and lower ribavirin concentrations (P = 0.02)
D'Avolio et al[127]	167	Italy	Retrospective	rs1127354 rs7270101	CHC/1	Peg-IFN + RBV	Both SNPs were associated with Hb decrease. The carrier of at least one variant in the ITPA was associated with a lower decrease of Hb (-1.1 g/dL), compared to patients without (-2.75 g/dL; P = 4.09 × 10)
Suzuki et al[133]	61	Japan	Retrospective cohort study	rs1127354	CHC/1	Peg-IFN + RBV + telaprevir	Decreases in Hb levels were greater in patients with CC than CA/AA genotypes at week 2 (-1.63 ± 0.92 g/dL vs -0.48 ± 0.75 g/dL, P = 0.001), week 4 (-3.5 ± 1.1 vs -2.2 ± 0.96, P = 0.001) and at the end of treatment (-2.9 ± 1.1 vs -2.0 ± 0.86, P = 0.013)
Ogawa et al[134]	292	Japan	Prospective, multicenter study	rs1127354	CHC/1	Peg-IFN + RBV + telaprevir	Pretreatment predictors of the development of severe anemia: baseline Hb < 135 g/L (HR = 2.53; P = 0.0013), estimated glomerular filtration rate < 80 mL/min per 1.73 m2 (HR = 1.83; P = 0.0265), ITPA CC genotype (rs1127354) (HR = 2.91; P = 0.0024)
Aghemo et al[135]	69	Italy	Retrospective cohort study	rs1127354 rs7270101	CHC/1	Peg-IFN + RBV + telaprevir	During the first 12 wk of TPV triple therapy: grade 3-4 anemia developed in 81% non-ITPA deficient patients vs 67% mildly deficient and 55% moderately deficient patients (P = NS); RBV dose reduction in 60% with no deficiency, 58% with mild, 67% with moderate deficiency (P = NS); Erythropoietin use in 65% with no deficiency, 58% with mild, 56% with moderate (P = NS); need for blood transfusion in 27% with no deficiency, 17% with mild, 33% with moderate (P = NS)

CHC: Chronic hepatitis C; Hb: Hemoglobin; RBV: Ribavirin; Peg-IFN: Peg-Interferon; SNP: Single nucleotide polymorphism; NS: Not significant.