Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population

Table 1 Demographic data for all groups

Groups	Sex(M/F)	P value1	P value2	Age (yr)	P value1	P value2
HBV infection	263/103	0.672		48.3 ± 11.8	0.657
HCC	64/30	0.713	0.345	48.8 ± 12.2	0.935	0.589
non-HCC	199/73	0.473		48.1 ± 11.7	0.544
Carrier	71/24	0.416		47.9 ± 11.3	0.570
CHB	58/18	0.310		46.5 ± 11.0	0.151
Cirrhosis	70/31	1.000		49.4 ± 12.6	0.621
Control	146/62			48.7 ± 11.3

¹vs control group;

²between HCC and non-HCC groups. HBV: Hepatitis B virus; HCC: Chronic HBV-infected patients with hepatocellular carcinoma; non-HCC: Chronic HBV-infected patients without hepatocellular carcinoma; Carrier: HBV carriers; CHB: Patients with chronic hepatitis B; Cirrhosis: Patients with HBV-related cirrhosis.

Table 2 Comparison of interleukin-21 polymorphisms between chronic hepatitis B virus-infected patients and controls n (%)

Polymorphism		HBV infection (n = 366)	Control (n = 208)	P value	OR (95%CI)
rs13143866
Allele frequency	Allele G	621 (85.5)	363 (87.3)		Reference
	Allele A	111 (14.5)	53 (12.7)	0.259	1.224 (0.861-1.741)
Genotype frequency1	GG	266 (72.7)	157 (75.5)		Reference
	GA	89 (24.3)	49 (23.5)	0.734	0.933 (0.625-1.392)
	AA	11 (3.0)	2 (1.0)	0.2902	0.308 (0.067-1.408)
	HWE	0.294	0.391
Recessive model	GG + GA	355 (97.0)	206 (99.0)		Reference
	AA	11 (3.0)	2 (1.0)	0.1492	3.195 (0.701-14.493)
Dominant model	GG	266 (72.7)	157 (75.5)		Reference
	AA + GA	100 (27.3)	51 (24.5)	0.463	1.157 (0.783-1.711)
rs2221903
Allele frequency	Allele T	632 (86.3)	373 (89.7)		Reference
	Allele C	100 (13.7)	43 (10.3)	0.101	1.373 (0.939-2.006)
Genotype frequency1	TT	272 (74.3)	167 (80.3)		Reference
	TC	88 (24.1)	39 (18.7)	0.130	1.385 (0.907-2.116)
	CC	6 (1.6)	2 (1.0)	0.2622	1.842 (0.367-9.232)
	HWE	0.712	0.868
Recessive model	TT+TC	360 (98.4)	206 (99.0)		Reference
	CC	6 (1.6)	2 (1.0)	0.7172	1.715 (0.342-8.547)
Dominant model	TT	272 (74.3)	167 (80.3)		Reference
	CC + TC	94 (25.7)	41 (19.7)	0.105	1.408 (0.930-2.130)
rs907715
Allele frequency	Allele G	415 (56.7)	234 (56.2)		Reference
	Allele A	317 (43.3)	182 (43.8)	0.884	0.982 (0.770-1.252)
Genotype frequency1	GG	110 (30.0)	70 (33.7)		Reference
	GA	195 (53.3)	94 (45.2)	0.160	1.320 (0.896-1.945)
	AA	61 (16.7)	44 (21.1)	0.155	0.882 (0.540-1.440)
	HWE	0.104	0.238
Recessive model	GG + GA	305 (83.3)	164 (78.8)		Reference
	AA	61 (16.7)	44 (21.2)	0.181	0.746 (0.484-1.148)
Dominant model	GG	110 (30.1)	70 (33.7)		Reference
	AA + GA	256 (69.9)	138 (66.3)	0.372	1.181 (0.820-1.699)

¹The P values of rs13143866, rs2221903, and rs907715 genotype distribution between chronic HBV-infected patients and controls were 0.237, 0.876, 0.358, respectively;

²Fisher’s exact test. HWE: Hardy-Weinberg equilibrium.

Table 3 Interleukin-21 polymorphisms among chronic hepatitis B virus-infected patients with hepatocellular carcinoma, patients without hepatocellular carcinoma, and controls n (%)

Polymorphism		HCC	non-HCC	Control	HCC vs non-HCC		HCC vs Control		non-HCC vs Control
		(n = 94)	(n = 272)	(n = 208)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)
rs13143866
Allele frequency	Allele G	167 (88.8)	454 (83.5)	363 (87.3)		Reference		Reference		Reference
	Allele A	21 (11.2)	90 (16.5)	53 (12.7)	0.078	1.576 (0.949-2.617)	0.586	0.861 (0.503-1.474)	0.102	1.358 (0.941-1.958)
Genotype frequency1	GG	74 (78.7)	192 (70.6)	157 (75.5)		Reference		Reference		Reference
	GA	19 (20.2)	70 (25.7)	49 (23.5)	0.231	1.420 (0.800-2.520)	0.522	0.823 (0.453-1.495)	0.470	1.168 (0.766-1.781)
	AA	1 (1.1)	10 (3.7)	2 (1.0)	0.2982	3.854 (0.485-30.637)	1.0002	1.061 (0.095-11.886)	0.0741	4.089 (0.883-18.934)
	HWE	0.857	0.262	0.391
Recessive model	GG + GA	93 (98.9)	262 (96.3)	206 (99.0)		Reference		Reference		Reference
	AA	1 (1.1)	10 (3.7)	2 (1.0)	0.2302	0.282 (0.036-2.231)	1.0002	1.108 (0.099-12.367)	0.0771	3.931 (0.852-18.139)
Dominant model	GG	74 (78.7)	192 (70.6)	157 (75.5)		Reference		Reference		Reference
	AA + GA	20 (21.3)	80 (29.4)	51 (24.5)	0.129	1.542 (0.882-2.695)	0.539	0.832 (0.463-1.495)	0.234	1.283 (0.852-1.932)
rs2221903
Allele frequency	Allele T	163 (86.7)	469 (86.2)	373 (89.7)		Reference		Reference		Reference
	Allele C	25 (13.3)	75 (13.8)	43 (10.3)	0.866	1.043 (0.641-1.696)	0.288	1.330 (0.786-2.252)	0.108	1.387 (0.931-2.067)
Genotype frequency1	TT	70 (74.5)	202 (74.3)	167 (80.3)		Reference		Reference		Reference
	TC	23 (24.5)	65 (23.9)	39 (18.7)	0.940	0.979 (0.566-1.694)	0.075	1.668 (0.949-2.932)	0.160	1.378 (0.881-2.154)
	CC	1 (1.1)	5 (1.8)	2 (1.0)	0.6962	1.733 (0.199-15.087)	1.0002	1.193 (0.106-13.369)	0.4661	2.067 (0.396-10.790)
	HWE	0.554	0.931	0.868
Recessive model	TT + TC	93 (98.9)	267 (98.2)	206 (99.0)		Reference		Reference		Reference
	CC	1 (1.1)	5 (1.8)	2 (1.0)	0.6962	1.742 (0.201-15.101)	1.0002	1.108 (0.099-12.367)	0.4791	1.929 (0.700-10.042)
Dominant model	TT	70 (74.5)	202 (74.3)	167 (80.3)		Reference		Reference		Reference
	CC + TC	24 (25.5)	70 (25.7)	41 (19.7)	0.969	0.989 (0.578-1.693)	0.256	1.397 (0.785-2.484)	0.122	1.411 (0.912-2.184)
rs907715
Allele frequency	Allele G	106 (56.4)	309 (56.8)	234 (56.2)		Reference		Reference		Reference
	Allele A	82 (43.6)	235 (43.2)	182 (43.8)	0.920	0.983 (0.704-1.374)	0.976	0.995 (0.703-1.408)	0.864	0.978 (0.756-1.265)
Genotype frequency1	GG	25 (26.6)	85 (31.2)	70 (33.7)		Reference		Reference		Reference
	GA	56 (59.6)	139 (51.1)	94 (45.2)	0.256	0.730 (0.424-1.257)	0.135	0.598 (0.305-1.173)	0.347	1.218 (0.808-1.836)
	AA	13 (13.8)	48 (17.7)	44 (21.1)	0.831	1.086 (0.509-2.317)	0.062	0.827 (0.383-1.785)	0.685	0.898 (0.536-1.507)
	HWE	0.041	0.496	0.238
Recessive model	GG + GA	81 (86.2)	224 (82.4)	164 (78.8)		Reference		Reference		Reference
	AA	13 (13.8)	48 (17.6)	44 (21.2)	0.393	1.335 (0.688-2.592)	0.135	0.598 (0.305-1.173)	0.334	0.799 (0.506-1.260)
Dominant model	GG	25 (26.6)	85 (31.3)	70 (33.7)		Reference		Reference		Reference
	AA + GA	69 (73.4)	187 (68.7)	138 (66.3)	0.397	0.797 (0.472-1.347)	0.222	1.400 (0.816-2.403)	0.577	1.116 (0.759-1.640)

¹The P values of rs13143866, rs2221903, and rs907715 genotype distribution among hepatocellular carcinoma (HCC) group, non-HCC group, and controls were 0.237, 0.876, and 0.358, respectively;

²Fisher’s exact test. HWE: Hardy-Weinberg equilibrium.

Table 4 Interleukin-21 polymorphisms among non-hepatocellular carcinoma subgroups and controls n (%)

Polymorphism		Carrier	CHB	Cirrhosis	Control	Carrier vs control		CHB vs control		Cirrhosis vs control
		(n = 101)	(n = 76)	(n = 95)	(n = 208)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)
rs13143866
Allele frequency	Allele G	170 (84.2)	128 (84.2)	156 (82.1)	363 (87.3)		Reference		Reference		Reference
	Allele A	32 (15.8)	24 (15.8)	34 (17.9)	53 (12.7)	0.294	1.289 (0.802-2.073)	0.348	1.284 (0.761-2.166)	0.095	1.493 (0.933-2.388)
Genotype frequency	GG	75 (74.3)	53 (69.7)	64 (67.4)	157 (75.5)		Reference		Reference		Reference
	GA	20 (19.8)	22 (28.9)	28 (29.5)	49 (23.5)	0.600	0.854 (0.474-1.539)	0.345	1.330 (0.736-2.403)	0.227	1.402 (0.811-2.424)
	AA	6 (5.9)	1 (1.3)	3 (3.1)	2 (1.0)	0.0191	6.280 (1.238-31.854)	1.0001	1.481 (0.132-16.666)	0.1561	3.680 (0.601-22.544)
	HWE	0.01	0.44	0.977	0.391
Recessive model	GG + GA	95 (94.1)	75 (98.7)	92 (96.8)	206 (99.0)		Reference		Reference		Reference
	AA	6 (5.9)	1 (1.3)	3 (3.2)	2 (1.0)	0.0171	6.505 (1.289-32.828)	1.0001	1.373 (0.123-15.367)	0.3301	3.359 (0.552-20.441)
Dominant model	GG	75 (74.3)	53 (69.7)	64 (67.4)	157 (75.5)		Reference		Reference		Reference
	AA + GA	26 (25.7)	23 (30.3)	31 (32.6)	51 (24.5)	0.816	1.067 (0.618-1.843)	0.330	1.336 (0.746-2.392)	0.142	1.491 (0.875-2.540)
rs2221903
Allele frequency	Allele T	172 (85.1)	130 (85.5)	167 (87.9)	373 (89.7)		Reference		Reference		Reference
	Allele C	30 (14.9)	22 (14.5)	23 (12.1)	43 (10.3)	0.105	1.513 (0.918-2.495)	0.172	1.468 (0.846-2.547)	0.517	1.195 (0.697-2.046)
Genotype frequency	TT	71 (70.3)	56 (73.7)	75 (78.9)	167 (80.3)		Reference		Reference		Reference
	TC	30 (29.7)	18 (23.7)	17 (17.9)	39 (18.7)	0.035	1.809 (1.043-3.139)	0.324	1.367 (0.729-2.598)	0.926	0.971 (0.516-1.825)
	CC	0 (0.00)	2 (2.6)	3 (3.2)	2 (1.0)	-2		0.5751	2.982 (0.410-21.668)	0.3301	3.340 (0.547-20.405)
	HWE	0.080	0.705	0.121	0.868
Recessive model	TT + TC	101 (100.0)	74 (97.4)	92 (96.8)	206 (99.0)		Reference		Reference		Reference
	CC	0 (0.0)	2 (2.6)	3 (3.2)	2 (1.0)	-2		0.5771	2.784 (0.385-20.120)	0.3301	3.359 (0.552-20.441)
Dominant model	TT	71 (70.3)	56 (73.7)	75 (78.9)	167 (80.3)		Reference		Reference		Reference
	CC + TC	30 (29.7)	20 (26.3)	20 (21.1)	41 (19.7)	0.052	1.721 (0.996-2.973)	0.232	1.455 (0.787-2.689)	0.787	1.086 (0.596-1.979)
rs907715
Allele frequency	Allele G	115 (56.9)	89 (58.6)	105 (55.3)	234 (56.2)		Reference		Reference		Reference
	Allele A	87 (43.8)	63 (41.4)	85 (44.7)	182 (43.8)	0.873	0.973 (0.693-1.366)	0.624	0.910 (0.625-1.326)	0.820	1.041 (0.737-1.470)
Genotype frequency	GG	33 (32.7)	24 (3.16)	28 (29.5)	70 (33.7)		Reference		Reference		Reference
	GA	49 (48.5)	41 (53.9)	49 (51.6)	94 (45.2)	0.715	1.106 (0.645-1.896)	0.425	1.272 (0.704-2.298)	0.352	1.303 (0.746-2.277)
	AA	19 (18.8)	11 (14.5)	18 (18.9)	44 (21.1)	0.800	0.916 (0.465-1.806)	0.443	0.729 (0.325-1.634)	0.950	1.023 (0.507-2.064)
	HWE	0.914	0.331	0.674	0.238
Recessive model	GG + GA	82 (81.2)	65 (85.5)	77 (81.1)	164 (78.8)		Reference		Reference		Reference
	AA	19 (18.8)	11 (14.5)	18 (18.9)	44 (21.2)	0.632	0.864 (0.474-1.573)	0.210	0.631 (0.307-1.296)	0.659	0.871 (0.473-1.606)
Dominant model	GG	33 (32.7)	24 (31.6)	28 (29.5)	70 (33.7)		Reference		Reference		Reference
	AA + GA	68 (67.3)	52 (68.4)	67 (70.5)	138 (66.3)	0.864	1.045 (0.630-1.733)	0.742	1.099 (0.626-1.929)	0.471	1.214 (0.717-2.055)

¹Fisher’s exact test;

²χ² test cannot be conducted due to cross tabulation of zero. CHB: Chronic hepatitis B; HWE: Hardy-Weinberg equilibrium.

Table 5 Haplotype analysis of polymorphisms

Haplotype1	Frequency		χ2	P value	OR	95%CI
	HBV infection	Control
A-T-A	0.150	0.127	1.117	0.291	1.209	0.850-1.720
G-C-G	0.137	0.103	2.725	0.099	1.376	0.941-2.011
G-T-A	0.283	0.31	0.883	0.347	0.882	0.678-1.147
G-T-G	0.429	0.459	0.959	0.327	0.886	0.695-1.129
	HCC	non-HCC
A-T-A	0.165	0.104	4.057	0.044	1.700	1.010-2.863
G-C-G	0.138	0.133	0.017	0.900	1.033	0.635-1.681
G-T-A	0.267	0.333	3.226	0.072	0.072	0.503-1.031
G-T-G	0.430	0.423	0.009	0.926	1.016	0.726-1.422

¹Haplotype of rs13143866 (G/A), rs2221903 (T/C), and rs907715 (G/A). HBV: Hepatitis B virus; HCC: Chronic HBV-infected patients with hepatocellular carcinoma; non-HCC: Chronic HBV-infected patients without hepatocellular carcinoma.