Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

Table 1 Clinical profiles of 242 healthy individuals and 379 hepatitis B virus-infected patients

Characteristics	HC (n = 242)	CHB (n = 99)	LC (n = 131)	HCC (n = 149)	P values
Age (yr)	39 (18-79)	41 (19-78)	52 (17-78)	53 (18-79)	< 0.0001
Gender (Male/Female)	156/86	82/17	105/26	119/30	< 0.0001
AST (IU/L)	NR	219 (17-3732)	74 (12-720)	59 (16-513)	< 0.0001
ALT (IU/L)	NR	158 (12-4593)	59 (9-1354)	47 (13-471)	< 0.0001
Total bilirubin (µmol/L)	NR	46.6 (1.8-795)	31 (1.2-722)	17 (2-290)	< 0.0001
Direct bilirubin (µmol/L)	NR	29.9 (1-512)	17 (1-450)	7.1 (1.2-189)	< 0.0001
Albumin (g/L)	NR	42 (23-48)	30 (20-47)	39 (27-49)	< 0.0001
Prothrombin (% of standard)	NR	85 (50-120)	47.5 (15-101)	80 (31-115)	< 0.0001
HBV-DNA (copies/mL)	NA	1.8 × 105 (4 × 102-8.1 × 106)	8.3 × 104 (2 × 102-4.1 × 106)	9.4 × 104 (2.9 × 102-1.0 × 105)	NS
Alfa Feto Protein (IU/L)	NR	4.3 (1.5-300)	8.6 (1.2-400)	196 (1.1- 438)	< 0.0001

CHB: Chronic hepatitis B; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; PLT: Platelets; AST and ALT: Aspartate and alanine amino transferase; IU: International unit; NS: Not significant; NA: Not applicable. NR: Normal range.

Table 2 Association of IRF5 rs13242262A/T and rs10488630A/G with hepatitis B virus-related liver cirrhosis n (%)

IRF5 variants	HC, n = 242	CHB, n = 99	LC, n = 131	HCC, n = 149	LC vs CHB
					OR (95%CI)	P value
rs13242262 A/T
AA	67 (27.7)	27 (27.3)	32 (24.4)	45 (30.2)	Reference
AT	119 (49.2)	59 (59.6)	65 (49.6)	77 (51.7)	1.0 (0.5-2.0)	NS
TT	56 (23.1)	13 (13.1)	34 (26.0)	27 (18.1)	3.1 (1.2-7.8)	0.014
Allele
A	253 (52.3)	113 (57)	129 (49.2)	165 (55.3)	Reference
T	231 (47.7)	85 (43)	133 (50.8)	133 (44.7)	1.5 (1.1-2.3)	0.040
Dominant
AA	67 (27.7)	27 (27.3)	32(24.4)	45 (30.2)	Reference
AT + TT	175 (72.3)	72 (72.7)	99 (75.6)	104 (69.8)	1.3 (0.7-2.6)	NS
Recessive
AA + AT	186 (76.9)	86 (87)	97 (74.0)	122 (81.9)	Reference
TT	56 (23.1)	13 (13)	34 (26.0)	27 (18.1)	2.8 (1.3-5.9)	0.0057
rs10488630 A/G
AA	115 (47.5)	58 (58.6)	59 (45.1)	73 (49.0)	Reference
AG	104 (43.0)	36 (36.4)	56 (42.7)	63 (42.3)	1.6 (0.9-2.9)	0.100
GG	23 (9.5)	5 (5.0)	16 (12.2)	13 (8.7)	3.0 (1.0-9.5)	0.045
Allele
A	334 (69)	152 (76.8)	174 (66.4)	209 (72.3)	Reference
G	150 (31)	46 (23.2)	88 (33.6)	89 (27.7)	1.7 (1.1-2.6)	0.019
Dominant
AA	115 (47.5)	58 (58.6)	59 (45.0)	73 (49)	Reference
AG + GG	127 (52.5)	41 (41.4)	72 (55.0)	76 (51)	1.8 (1.0-3.2)	0.035
Recessive
AA + AG	219 (90.5)	94 (94.9)	115 (87.8)	136 (91.3)	Reference
GG	23 (9.5)	5 (5.1)	16 (12.2)	13 (7.8)	2.4 (0.8-7.2)	0.100

HC: Healthy controls; CHB: Chronic hepatitis B; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma.

Table 3 Allele and genotype frequencies of IRF5 rs77416878C/T and rs2280714T/C in Vietnamese patients with hepatitis B virus-related liver diseases n (%)

IRF5 variants	HC,n = 242	CHB,n = 99	LC,n = 131	HCC,n = 149
rs77416878
CC	192 (79.4)	79 (79.8)	98 (74.8)	115 (77.2)
CT	48 (19.8)	19 (19.2)	32 (24.4)	31 (20.8)
TT	2 (0.8)	1 (1)	1 (0.8)	3 (2)
Allele
C	432 (89.3)	177 (89.4)	228 (87)	261 (87.6)
T	52 (10.7)	21 (10.6)	34 (13)	37 (12.4)
Dominant
CC	192 (79.4)	79 (79.8)	98 (74.8)	115 (77.2)
CT + TT	50 (20.6)	20 (20.2)	33 (24.4)	34 (22.8)
Recessive
CC + CT	240 (99.2)	98 (99)	130 (99.2)	146 (98)
TT	2 (0.8)	1 (1)	1 (0.8)	3 (2)
rs2280714
TT	84 (34.7)	31 (31.3)	47 (35.9)	39 (26.2)
TC	114 (47.1)	52 (52.5)	69 (52.7)	87 (58.4)
CC	44 (18.2)	16 (16.2)	15 (11.4)	23 (15.4)
Allele
T	282 (58.3)	114 (57.6)	163 (62.2)	165 (55.4)
C	202 (41.7)	84 (42.4)	99 (37.8)	133 (44.6)
Dominant
TT	84 (34.7)	31 (31.3)	47 (35.9)	39 (26.2)
TC + TT	158 (65.3)	78 (68.7)	84 (64.1)	110 (73.8)
Recessive
TT + TC	198 (81.8)	83 (83.8)	116 (88.6)	126 (84.6)
CC	44 (18.2)	16 (16.2)	15 (11.4)	23 (15.4)

HC: Healthy controls; CHB: Chronic hepatitis B; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma. All comparisons between groups using binary logistic model adjusted for age and gen did not indicate a significant difference (adjusted P > 0.05, data not shown in this table).

Table 4 Haplotype distribution among chronic hepatitis B virus carriers and the association of IRF5 haplotypes with hepatitis B virus-infected liver diseases n (%)

Haplotypes	HC,n = 484	CHB,n = 198	LC,n = 298	HCC,n = 262	LC vs CHB		HCC vs CHB		HCC vs LC
					OR (95% CI)	P value	OR (95% CI)	P value	OR (95%CI)	P value
ACAC	196 (40.6)	83 (41.9)	98 (37.4)	132 (44.3)	Reference		Reference		Reference
TCGT	141 (29.0)	37 (18.7)	86 (32.7)	81 (27.2)	2.1 (1.2-3.3)	0.008		NS	0.7 (0.4-1.1)	0.08
TCAT	33 (6.8)	27 (13.6)	12 (4.6)	13 (4.4)	0.4 (0.2-0.8)	0.037	0.3 (0.15-0.7)	0.003		NS
ACAT	54 (11.2)	24 (12)	30 (11.5)	31 (10.4)		NS		NS		NS
TTAT	49 (10.2)	18 (9.1)	34 (13)	33 (11.1)		NS		NS		NS
ACGC	2 (0.4)	1 (0.5)	0 (0)	1 (0.3)		NS		NS		NS
ACGT	5 (1)	5 (2.5)	1 (0.4)	3 (1)		NS		NS		NS
TCGC	2 (0.4)	0 (0)	1 (0.4)	0 (0)		NS		NS		NS
TTGT	2 (0.4)	3 (1.5)	0 (0)	4 (1.3)		NS		NS		NS

HCC: Hepatocellular carcinoma. Comparison between HC vs HBV patient group did not indicate any significant difference (data not shown in this table). OR and P values were calculated by using binary logistic model adjusted for age and gender, CHB: Chronic hepatitis B; LC: Liver cirrhosis.