Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

Table 1 List of primers used in the study

DQB1 allele	Primers	PCR product	DRB1 allele	Primers	PCR product
DQB1*0501	5’ 5’ CGGAGCGCGTGCGGGG 3’	128	DRB1*01	5’ TTGTGGCAGCTTAAGTTTGAAT 3’	168
	3’ 5’ GCTGTTCCAGTACTCGGCAA 3’			5’ GCTGTTCCAGTACTCGGCAT 3’
DQB1*0502	5’ 5’ TGCGGGGTGTGACCAGAC 3’	117	DRB1*15/16	5’ TCCTGTGGCAGCCTAAGA G 3’	310
	3’ 5’ TGTTCCAGTACTCGGCGCT 3’			5’ CGCTGCACTGTGAAGCTCTC 3’
DQB1*0503	5’ 5’ TGCGGGGTGTGACCAGAC 3’	87	DRB1*03	5’ GTTTCTTGGAGTACTCTAGGTC 3’	222
	3’ 5’ GCGGCGTCACCGCCCGA 3’			5’ TGCAGTAGTTGTCCACCCG 3’
DQB1*0601	5’ 5’ GCCATGTGCTACTTCACCAAT 3’	198	DRB1*04	5’ GTTTCTTGGAGCAGGTTAAACA 3’	262
	3’ 5’ CACCGTGTCCAACTCCGCT 3’			5’ CGCTGCACTGTGAAGCTCTC 3’
DQB1*0602	5’ 5’ CGTGCGTCTTGTGACCAGAT 3’	121	DRB1*11	5’ CACGTTTCTTGGAGTACTCTAC 3’	179
	3’ 5’ GCTGTTCCAGTACTCGGCAT 3’			5’ CTGGCTGTTCCAGTACTCCT 3’
DQB1*0603	5’ 5’ GGAGCGCGTGCGTCTTGTA 3’	127	DRB1*12	5’ AGTACTCTACGGGTGAGTGTT 3’	198
	3’ 5’ GCTGTTCCAGTACTCGGCAT 3’			5’ CTGTTCCAGGACTCGGCGA 3’
DQB1*0604	5’ 5’ CGTGTACCAGTTTAAGGGCA 3’	254	DRB1*13/14	5’ GTTTCTTGGAGTACTCTACGTC 3’	234
	3’ 5’ GCAGGATCCCGCGGTACC 3’			5’ CGTAGTTGTGTCTGCA(GA)TAGG 3’
DQB1*0201	5’ 5’ GTGCGTATTGTGAGCAGAAG 3’	205	DRB1*07	5’ CCTGTGGCAGGG AAGTATA 3’	232
	3’ 5’ GCAAGGTCGTGCGGAGCT 3’			5’ CCCGTAGTTGTGTCTGCACAC 3’
DQB1*0201/0302	5’ 5’ GACGGAGCGCGTGCGTCT 3’	129	DRB1*08	5’ AGTACTCTACGGGTGAGTGTT 3’	227
	3’ 5’ CTGTTCCAGTACTCGGCGG 3’			5’ CCCGTATTGTGTCTGCAG 3’
DQB1*0301	5’ 5’ GACGGAGCGCGTGCGTTA 3’	122	DRB1*09	5’ GTTTCTTGAAGCAGGATAAGTTT 3’	236
	3’ 5’ AGTACTCGGCGTCAGGCG 3’			5’ CCCGTAGTTGTGTCTGCACAC 3’
DQB1*0302/0303	5’ 5’ GACGGAGCGCGTGCGTCT 3’	122	DRB1*10	5’ CGGTTGCTGGAAAGACGCG 3’	204
	3’ 5’ AGTACTCGGCGTCAGGCG 3’			5’ CTGCACTGTGAAGCT CTCAC 3’
DQB1*0303	5’ 5’ GACGGAGCGCGTGCGTCT 3’	129	DRB1-Exon2	5’ TTCGTGTCCCCACAGCACGTTTC 3’	295
	3’ 5’ CTGTTCCAGTACTCGGCGT 3’			5’ GCCGCTGCACTGTGAAGCTCTC 3’
DQB1*0401	5’ 5’ CACCAACGGGACCGAGCT 3’	200	Internal control (HGH)	5′ CAGTGCCTTCCCAACCATTCCCTTA 3′	439
	3’ 5’ GGTAGTTGTGTCTGCATACG 3’			5’ ATCCACTCACGGATTTCTGTTGTGTTTC 3′
DQB1*0402	5’ 5’ CACCAACGGGACCGAGCG 3’	200
	3’ 5’ GGTAGTTGTGTCTGCATACG 3’

Table 2 DQB1 alleles among patients with active disease or inactive disease n (%)

	DQB1 allele	Patients with active disease	Patients with inactive disease	χ2	P value	OR	95%CI
		n = 289	n = 66
1	*05:01	78 (27)	6 (9.1)	9.52	0.002a	3.7	1.5-8.9
2	*05:02	27 (9.3)	7 (10.6)	0.1	0.75	0.9	0.4-2.1
3	*05:03	53 (18.3)	14 (21.2)	0.29	0.59	0.83	0.4-1.6
4	*06:01	40 (13.8)	12 (18.2)	0.81	0.37	0.7	0.4-1.5
5	*06:02	0	0	NA	NA	NA	NA
6	*06:03	0	0	NA	NA	NA	NA
7	*06:04	1 (0.3)	1 (1.5)	b	0.34	0.2	0.01-3.7
8	*02:01	2 (0.7)	1 (1.5)	b	0.46	0.5	0.04-5.1
9	*03:02	94 (32.5)	20 (30.3)	0.12	0.72	1.1	0.6-2
10	*03:01	135 (46.7)	36 (54.5)	1.32	0.25	0.7	0.4-1.3
11	*03:03	27 (9.3)	5 (7.6)	0.2	0.65	1.3	0.4-3.4
12	*04:02	7 (2.4)	0	b	0.36	NA	NA
13	*04:01	0	0	NA	NA	NA	NA

^aP < 0.01 (after Bonferroni correction). b: Fisher’s exact test was applied; NA: Not available.

Table 3 DRB1 alleles among patients with cirrhosis or without cirrhosis n (%)

	DRB1 allele	Patients with cirrhosis n = 87	Patients without cirrhosis n = 268	χ2	P value	OR	95%CI
1	*01	2 (2.3)	7 (2.6)	b	1	0.9	0.2-4.3
2	*15/16	17 (19.5)	56 (20.9)	0.07	0.79	0.9	0.5-1.7
3	*03	9 (10.3)	26 (9.7)	0.03	0.8	1.1	0.5-2.4
4	*04	2 (2.3)	3 (1.1)	b	0.6	2.1	0.3-12.7
5	*11	3(3.4)	6 (2.2)	b	0.5	1.5	0.4-6.4
6	*12	5 (5.7)	24 (9)	0.9	0.34	0.6	0.2-1.7
7	*13/14	45 (51.7)	139 (51.9)	0.01	0.98	1	0.6-1.6
8	*07	3 (3.4)	43 (16.0)	9.2	0.002a	0.2	0.06-0.6
9	*08	4 (4.6)	5 (1.9)	b	0.2	2.5	0.7-9.7
10	*09	3 (3.4)	4 (1.5)	b	0.37	2.3	0.5-10.7
11	*10	4 (4.6)	11 (4.1)	b	0.77	1.1	0.4-3.6

^aP < 0.05 (after Bonferroni correction). b: Fisher’s exact test was applied; NA: Not available.

Table 4 Factors affecting the presence of cirrhosis (multivariate logistic regression analysis)

	Beta	SE	Wald	Exp (Beta)	P value	95%CI
HBeAg (positive)	-0.08	0.38	0.05	0.92	0.83	0.44-1.93
DRB1*07	-1.59	0.65	5.9	0.2	0.015	0.06-0.73
Age at diagnosis	0.07	0.01	39.9	1.07	< 0.001	1.05-1.09
Gender (male)	0.78	0.30	6.7	2.18	0.01	1.2-3.9

HBeAg: Hepatitis B early antigen.