Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: A meta-analysis

Table 1 Main characteristics of case-control studies included in this systematic review and meta-analysis

No.	Study	Yr	Language	Ethnicity	Genotyping	Spontaneously recovered control		Chronic hepatitis B case		NOS score
						n	Characteristics	n	Characteristics
1	Thursz et al[32]	1995	English	Gambia	PCR-RFLP	413	218 children; 195 adults	225	185 children; 40 adults	7
2	Hohler et al[16]	1997	English	Caucasian	PCR-SSP	24	NA	70	Outpatients	7
3	Ahn et al[18]	2000	English	Korean	PCR-SSP	243	156 males, mean age: 41 yr	83	53 males, mean age: 35 yr	8
4	Chen et al[42]	2002	Chinese	Chinese Han	PCR-SSP	56	43 males, mean age: 47.6 yr	30	22 males, mean age: 38.7 yr	7
5	Akcam et al[33]	2002	English	Iran	PCR-SSP	30	20 males, mean age: 35.9 yr	30	7 males, mean age: 31.0 yr	7
6	Jiang et al[21]	2003	English	Chinese Han	PCR-SSP	30	24 males, mean age: 33.2 yr	52	43 males, mean age: 33.46 yr	7
7	Meng et al[20]	2003	English	Chinese Han	PCR-SSP	56	22 males, mean age: 38.7 yr	30	43 males, mean age: 47.6 yr	7
8	Wu et al[19]	2004	English	Chinese Han	SSOPH	324	169 males, mean age: 39.1 yr	98	66 males, mean age: 50.9 yr	8
9	Wu et al[19]	2004	English	Taiwanese aborigines	SSOPH	229	90 males, mean age: 52.1 yr	138	60 males, mean age: 45.7 yr	8
10	Lu et al[43]	2006	Chinese	Chinese Han	PCR-SSP	148	70 males, mean age: 37.75 yr	417	289 males; 207 CHB, 212ASC ASC	6
11	Zhang et al[34]	2006	English	Chinese Han	PCR-SSP	32	20 males, mean age: 38.4 yr	61	40 males, mean age: 38.4 yr	7
14	Yang et al[35]	2007	English	Chinese Han	PCR-SSP	108	Age and sex matched	108	90 males, 58 LC, 24 HCC	7
15	Song et al[44]	2007	Chinese	Chinese Han	PCR-SSP	102	63 males, mean age: 33.9 yr	276	168 males, 77 LC, 106 ASC	5
14	Zhu et al[36]	2007	English	Chinese Han	PCR-SSP	133	63 males, mean age: 37 yr	151	120 males, mean age: 40 yr	7
15	Hwang et al[37]	2007	English	Korean	PCR-SSP	438	286 man, mean age: 39 yr	198	148 males, 76 LC, 28 HCC	7
16	Kummee et al[38]	2007	English	Thai	PCR-SSP	100	48 males, mean age: 51.0 yr	150	80 males, mean age: 30.9 yr	8
17	Cho et al[39]	2008	English	Korean	PCR-SSP	80	60 males, mean age: 47.9 yr	384	283 males, mean age: 41.0 yr	8
18	Remezani et al[40]	2008	English	Iran	PCR-SSP	30	17 males, mean age: 32.2 yr	33	20 males, mean age: 38 yr	8
19	Albayrak et al[41]	2011	English	Turkish	PCR-SSP	30	15 males, mean age: 33.9 yr	75	48 males, mean age: 33.0 yr	8

NA: Relative data were not available in original studies; PCR-RFLP: Polymerase chain reaction-restriction fragment length polymorphism; PCR-SSP: Polymerase chain reaction sequence specific primers; PCR-SSO: Polymerase chain reaction sequence specific oligonucleotide probe; SSOPH: Sequence-specific oligonucleotide probe hybridization: CHB: Chronic hepatitis B; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; ASC: Asymptomatic hepatitis B virus carriers; NOS: Newcastle-Ottawa Scale.

Table 2 Meta-analysis of relationship between human leukocyte antigens-DR gene polymorphism and clearance of persistent hepatitis B virus infection

Allele	Present vs null	StudiesNo.	SRC (n/N)	CHB (n/N)	Heterogeneity		M	OR		Publication bias
					I2 (%)	PH		OR (95% CI)	POR	Pbeggr’s	PEgger’s
DR*01	Total studies	13	109/1500	132/1673	0	0.826	F	0.69 (0.52-0.93)	0.016	0.143	0.221
	Chinese Han group	6	18/432	34/415	0	0.928	F	0.48 (0.26-0.86)	0.014	0.348	0.219
	Other ethnic groups	7	91/1068	98/1258	0	0.643	F	0.79 (0.56-1.12)	0.191	0.133	0.104
DR*03	Total studies	12	180/1489	177/1789	16.0	0.287	F	1.47 (1.16-1.87)	0.002	0.945	0.572
	Chinese Han group	5	72/470	74/627	37.0	0.174	F	1.57 (1.07-2.30)	0.020	0.806	0.838
	Other ethnic groups	7	108/1019	103/1162	8.6	0.363	F	1.41 (1.03-1.91)	0.029	0.548	0.444
DR*04	Total studies	16	358/1766	549/2256	0	0.757	F	0.72 (0.60-0.85)	0.000	0.207	0.255
	Chinese Han group	7	104/530	215/739	0	0.920	F	0.63 (0.48-0.84)	0.002	0.453	0.299
	Other ethnic groups	9	254/1236	334/1517	0	0.459	F	0.77 (0.62-0.95)	0.016	0.175	0.178
DR*07	Total studies	13	239/1373	146/1584	14	0.304	F	1.59 (1.24-2.03)	0.000	0.625	0.634
	Chinese Han group	7	111/530	82/739	13.6	0.326	F	1.50 (1.07-2.10)	0.017	0.881	0.601
	Other ethnic groups	6	128/843	64/845	27.7	0.227	F	1.69 (1.17-2.44)	0.005	0.452	0.924
DR*08	Total studies	15	290/1736	301/2226	0	0.541	F	1.19 (0.98-1.44)	0.083	0.255	0.250
	Chinese Han group	7	105/530	124/739	0	0.850	F	1.30 (0.96-1.77)	0.086	0.293	0.188
	Other ethnic groups	8	185/1206	177/1487	27.7	0.207	F	1.11 (0.86-1.43)	0.409	0.711	0.447
DR*09	Total studies	14	344/1703	385/2196	33.3	0.108	F	1.17 (0.98-1.40)	0.075	0.661	0.740
	Chinese Han group	7	157/530	206/739	32.3	0.182	F	1.10 (0.85-1.42)	0.467	0.230	0.241
	Other ethnic groups	7	187/1173	179/1457	40.7	0.120	F	1.25 (0.98-1.59)	0.077	0.764	0.786
DR*10	Total studies	11	62/955	96/1447	0	0.921	F	1.08 (0.76-1.53)	0.682	0.815	0.343
	Chinese Han group	6	9/469	24/707	0	0.871	F	0.68 (0.29-1.49)	0.314	0.039	0.040
	Other ethnic groups	5	51/1206	70/1487	0	0.860	F	1.22 (0.82-1.81)	0.325	0.806	0.687
DR*11	Total studies	14	221/1459	229/1630	41.3	0.053	R	1.03 (0.75-1.42)	0.839	0.477	0.915
	Chinese Han group	7	73/530	107/739	59.1	0.023	R	1.08 (0.59-1.97)	0.806	0.652	0.848
	Other ethnic groups	7	148/929	122/891	20.0	0.277	F	1.00 (0.74-1.35)	0.993	0.548	0.953
DR*12	Total studies	12	336/1478	360/1590	30.1	0.152	F	1.08 (0.90-1.31)	0.406	0.945	0.948
	Chinese Han group	6	142/500	173/683	33.7	0.183	F	1.23 (0.93-1.62)	0.149	0.707	0.642
	Other ethnic groups	6	194/978	187/978	27.2	0.231	F	0.98 (0.76-1.26)	0.845	1.000	0.709
DR*13	Total studies	16	69/1779	211/2127	0	0.699	F	0.27 (0.19-0.37)	0.000	0.964	0.473
	Chinese Han group	7	12/531	48/739	0	0.867	F	0.36 (0.18-0.70)	0.003	0.368	0.510
	Other ethnic groups	9	57/1248	163/1388	1.3	0.424	F	0.24 (0.17-0.35)	0.000	0.175	0.017
DR*14	Total studies	14	281/1511	335/739	12.2	0.319	F	1.17 (0.94-1.46)	0.151	0.071	0.073
	Chinese Han group	7	73/530	97/739	0.2	0.422	F	1.11 (0.79-1.57)	0.552	0.176	0.108
	Other ethnic groups	7	208/981	238/1074	29.7	0.201	F	1.22 (0.92-1.62)	0.172	0.022	0.076
DR*15	Total studies	12	248/1230	236/1132	0	0.525	F	0.84 (0.67-1.05)	0.127	0.075	0.052
	Chinese Han group	7	113/530	161/739	13.2	0.329	F	0.92 (0.69-1.22)	0.556	0.293	0.155
	Other ethnic groups	5	135/700	75/393	0	0.717	F	0.73 (0.51-1.04)	0.084	0.221	0.133
DR*16	Total studies	12	41/876	78/1082	22.4	0.224	F	0.71 (0.47-1.06)	0.097	0.170	0.140
	Chinese Han group	7	24/530	59/739	12.7	0.333	F	0.60 (0.42-1.13)	0.137	0.652	0.042
	Other ethnic groups	5	17/346	19/343	44.8	0.124	F	0.76 (0.37-1.54)	0.447	0.221	0.764

M: Model of meta-analysis; F: Fixed-effects model; R: Random-effects model; PH: The P value for heterogeneity test; POR: The P value for OR test; Pbeggr’s: The P value for Egger’s test; PEgger’s: The P value for Egger’s test; CHB: Chronic hepatitis B; SRC: Spontaneously recovered control; OR: Odds ratio.