Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients

Table 1 Primer and probe of SNPs

SNPs		Primer and probe (5’-3’)
rs10903035	Forward primer	TTGCCACCCTTGACCTCAG
	Reverse primer	GAGGTTTTGTTTAGAGGGATCCAC
	Probe-FAM	TAGCAAACCACTCCTT
	Probe-HEX	TTAGCAAATCACTCCTT
rs11249006	Forward primer	AACTGGAAGGGAGAATGGGACT
	Reverse primer	GTAACATGGCAGGAATCGGACT
	Probe-FAM	CCACAACAGTCAACCA
	Probe-HEX	CACAACGGTCAACCA
rs2834167	Forward primer	TACCACCTCCCGAAAATGTCA
	Reverse primer	GGTGCGTTCCTGCCAATAGT
	Probe-FAM	TTCCCTTTGGCAAAAG
	Probe-HEX	TTCCCTTCGGCAAAA
rs2071430	Forward primer	CCGAGAACCTGCGTCTCC
	Reverse primer	CGCGAAGAAATGAAACTCACAGAC
	Probe-FAM	CGTTTCTGCGCCCG
	Probe-HEX	CGTTTCTGCTCCCG
rs17000900	Forward primer	CCGAGAACCTGCGTCTCC
	Reverse primer	CGCGAAGAAATGAAACTCACAGAC
	Probe-FAM	CAAGTGCTGCAGGTG
	Probe-HEX	CAAGTGCTGAAGGTG
rs12980275	Forward primer	TGAGGTGCTGAGAGAAGTCAAATT
	Reverse primer	CGCTACCCCGGCAAATATT
	Probe-FAM	CTAGAAACGGACGTGTC
	Probe-HEX	CTAGAAACAGACGTGTCT

Table 2 Baseline characteristics of participants n (%)

Variables	RVR(n = 133)	NRVR(n = 105)	P value
Age (yr)
≤ 50	51 (38.35)	40 (38.10)
> 50	82 (61.65)	65 (61.90)	0.968
Sex
Male	41 (30.83)	21 (20.00)
Female	92 (69.17)	84 (80.00)	0.059
HCV genotype
1a/1b	93 (69.92)	70 (66.67)
3	14 (10.53)	5 (4.76)
Mixed	26 (19.55)	30 (28.57)	0.102
ALT (U/L)
≤ 40	64 (48.12)	28 (26.67)
(40-80]	38 (28.57)	42 (40.00)
> 80	30 (22.56)	35 (33.33)	0.003
ALB (g/L)
[40-55]	99 (74.44)	82 (78.10)
< 40	33 (24.81)	23 (21.90)	0.577
WBC (× 109/L)
[4-10]	75 (56.39)	73 (69.52)
< 4	57 (42.86)	31 (29.52)	0.035
> 10	1 (0.75)	1 (0.95)	0.985
PLT (× 109/L)
[100-300]	90 (67.67)	68 (64.76)
< 100	41 (30.83)	37 (35.24)	0.522
AFP (ng/mL)
≤ 7	95 (71.43)	68 (64.76)
> 7	19 (14.29)	30 (28.57)	0.016
HGB (g/L)
[110-150]	99 (74.44)	89 (84.76)
< 110	13 (9.77)	8 (7.62)
> 150	21 (15.79)	8 (7.62)	0.116
Baseline RNA (lg, IU/mL)	6.02 ± 0.97	6.19 ± 0.74	0.138

ALB: Albumin; HGB: Hemoglobin; PLT: Platelet; RVR: Rapid viral response; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; WBC: White blood cell; AFP: α-fetoprotein.

Table 3 Interferon-λ-related genes polymorphisms and rapid viral response n (%)

Genotype	RVR	NRVR	Crude OR (95%CI)	Adjusted OR (95%CI)
rs11249006	n = 133	n = 105
AA	51 (38.35)	49 (46.67)	1	1
AG	62 (46.62)	49 (46.67)	1.22 (0.71-2.09)	0.86 (0.45-1.63)
GG	20 (15.04)	7 (6.67)	2.75 (1.07-7.07)	2.33 (0.84-6.48)
Dominant			1.41 (0.84-2.36)	1.06 (0.58-1.94)
Recessive			2.48 (1.01-6.11)	2.52 (0.96-6.64)
Additive			1.47 (0.99-2.19)	1.27 (0.82-1.98)
rs12980275	n = 133	n = 105
AA	118 (88.72)	70 (66.67)	1	1
AG	8 (6.02)	28 (26.67)	0.17 (0.07-0.39)	0.11 (0.04-0.30)
GG	7 (5.26)	7 (6.67)	0.59 (0.20-1.76)	0.54 (0.17-1.74)
Dominant			0.25 (0.13-0.50)	0.19 (0.09-0.43)
Recessive			0.78 (0.26-2.29)	0.82 (0.26-2.56)
Additive			0.46 (0.28-0.76)	0.43 (0.24-0.75)
rs2834167	n = 133	n = 105
AA	37 (27.82)	28 (26.67)	1	1
AG	79 (59.40)	62 (59.05)	0.96 (0.53-1.74)	0.90 (0.45-1.78)
GG	17 (12.78)	15 (14.29)	0.86 (0.37-2.01)	0.66 (0.23-1.88)
Dominant			0.94 (0.53-1.68)	0.85 (0.44-1.66)
Recessive			0.88 (0.42-1.86)	0.71 (0.28-1.83)
Additive			0.93 (0.62-1.41)	0.83 (0.51-1.36)
rs10903035	n = 133	n = 105
AA	43 (32.33)	27 (25.71)	1	1
AG	56 (42.11)	48 (45.71)	0.73 (0.40-1.36)	0.68 (0.34-1.37)
GG	34 (32.28)	30 (28.57)	0.71 (0.36-1.42)	0.91 (0.41-2.02)
Dominant			0.72 (0.41-1.28)	0.76 (0.40-1.44)
Recessive			0.86 (0.48-1.53)	1.14 (0.58-2.25)
Additive			0.84 (0.60-1.19)	0.94 (0.63-1.40)
rs2071430	n = 127	n = 96
GG	63 (49.61)	49 (51.04)	1	1
GT	49 (38.58)	40 (41.67)	0.95 (0.54-1.67)	0.94 (0.50-1.80)
TT	15 (11.81)	7 (7.29)	1.67 (0.63-4.40)	2.13 (0.66-6.85)
Dominant			1.14 (0.68-1.91)	1.26 (0.70-2.28)
Recessive			1.78 (0.70-4.54)	2.28 (0.73-7.08)
Additive			1.15 (0.77-1.72)	1.21 (0.76-1.94)
rs17000900	n = 130	n = 99
AA	97 (74.62)	69 (69.70)	1	1
AG	29 (22.31)	27 (27.27)	0.76 (0.42-1.40)	0.79 (0.39-1.61)
GG	4 (3.08)	3 (3.03)	0.95 (0.21-4.38)	0.68 (0.13-3.70)
Dominant			0.83 (0.46-1.47)	0.83 (0.43-1.62)
Recessive			1.05 (0.23-4.82)	0.77 (0.14-4.16)
Additive			0.84 (0.51-1.38)	0.80 (0.45-1.42)

Logistic regression analyses adjusted for sex, ALT, WBC, AFP, HCV genotype and baseline viral load. RVR: Rapid viral response.

Table 4 Polymorphisms of IL28RA/IL28B and rapid viral response n (%)

Genotype	RVR (n = 133)	NRVR (n = 105)	Crude OR (95%CI)	P value	Adjusted OR (95%CI)	P value
rs11249006
AA	51 (38.35)	49 (46.67)	1		1
AG	62 (46.62)	49 (46.67)	1.22 (0.71-2.09)	0.048	0.86 (0.45-1.63)	0.637
GG	20 (15.04)	7 (6.67)	2.75 (1.07-7.07)	0.036	2.33 (0.84-6.48)	0.104
Dominant			1.41 (0.84-2.36)	0.197	1.06 (0.58-1.94)	0.852
Recessive			2.48 (1.01-6.11)	0.049	2.52 (0.96-6.64)	0.061
Additive			1.47 (0.99-2.19)	0.055	1.27 (0.82-1.98)	0.282
rs12980275
AA	118 (88.72)	70 (66.67)	1		1
AG	8 (6.02)	28 (26.67)	0.17 (0.07-0.39)	< 0.001	0.11 (0.04-0.30)	< 0.001
GG	7 (5.26)	7 (6.67)	0.59 (0.20-1.76)	0.347	0.54 (0.17-1.74)	0.301
Dominant			0.25 (0.13-0.50)	< 0.001	0.19 (0.09-0.43)	< 0.001
Recessive			0.78 (0.26-2.29)	0.648	0.82 (0.26-2.56)	0.736
Additive			0.46 (0.28-0.76)	0.002	0.43 (0.24-0.75)	0.003

Logistic regression analyses adjusted for sex, HCV genotype, baseline levels of ALT, WBC, AFP, and viral loads. RVR: Rapid viral response.

Table 5 Results of multivariate stepwise regression analysis on rapid viral response

Variable	Coef	OR (95%CI)	P value
rs12980275	-1.05	0.35 (0.20-0.62)	< 0.001
WBC-group	0.67	1.94 (1.08-3.50)	0.027
AFP-group	-0.98	0.38 (0.19-0.76)	0.006
HCV genotype	-0.39	0.67 (0.48-0.96)	0.014
Baseline RNA(lg)	-0.46	0.63 (0.44-0.91)	0.027

Coef: Coefficient of variation. WBC-group: WBC was divided into three groups. 1: 4 × 10⁹-10¹⁰/L; 2: < 4 × 109/L; 3: > 10¹⁰/L. AFP-group: AFP was divided into two groups. 1: ≤ 7 ng/mL; 2: > 7 ng/mL. RVR: Rapid viral response; HCV: Hepatitis C virus.