In silicoanalysis of HLA associations with drug-induced liver injury: use of a HLA-genotyped DNA archive from healthy volunteers

Table 1 HLA alleles associated with adverse drug reactions and cell availability in the HLA-typed archive

					Number of carriers of HLA alleles associated with DILI in our cohort (n= 385)
Drug	HLA allele	Reaction (ethnicity)	Odds ratio (95% CI)	Reference	Hmz	Htz
Drug-induced hypersensitivity reactions
Abacavir	B*57:01	Hypersensitivity (all)	117 (29-481)	[14]	1	25
Carbamazepine	B*15:02	SJS/TEN (Han Chinese)	2,504 (126-49,522)	[4]	1	6
	A*31:01	All phenotypes (Caucasian)	12.12 (4.03-20.65)	[17]	0	23
Allopurinol	B*58:01	SJS (Han Chinese)	580.3 (34.4-9,780.9)		0	6
		SJS (Caucasian)	80 (34-187)	[10, 12]
Nevirapine	DRB1*01:01	Hypersensitivity (Caucasian)	4.8 (1.3-16.8)	[16]	3	52
Lamotrigine	B*38	SJS/TEN (Caucasian)	6.8 (2.6-18)	[12]	0	7
Drug-induced liver injury
Flucloxacillin	B*57:01	DILI (Caucasian)	80.6 (22.8-284.9)	[6]	1	25
Ximelagatran	DRB1*07:01	DILI (Caucasian)	4.4 (2.2-8.9)	[11]	10	91
	DQA1*02:01		4.4 (2.2-8.1)		ND	ND
Lumiracoxib	DRB1*15:01	DILI (Caucasian)	7.5 (5.0 to 11.3)	[21]	10	100
	DQA1*01:02		6.3 (4.1 to 9.6)		ND	ND
	DQB1*06:02		6.9 (4.6 to 10.3)		8	90
Co-amoxiclav	DRB1*15:01 and	DILI (Caucasian)	2.8 (2.1 to 3.8)	[7, 8, 13, 18]	10	100
	DQB1*06:02				8	90
	A*02:01		2.3 (1.8 to 2.9)		46	153
Antituberculosis (isoniazid, rifampicin, pyrazinamide)	DQB1*02:01	DILI (Indian)	1.9 (1.0 to 3.9)	[20]	20	143
Lapatinib	DQA1*02:01	DILI (Caucasian)	2.2 (1.1 to 5.7)	[22]	ND	ND
			9.0 (3.2 to 27.4)
	DRB1*07:01		6.9 (2.5 to 19.9)		10	91
	DQB1*02:02		6.9 (2.5 to 19.6)		0	0
Diclofenac	DRB1*13	DILI (Caucasian)	-	[5]	-	-
Clometacin	B*08	DILI	-	[19]	-	-
Ticlopidine	A*33:03	DILI (Japanese)	13.0 (4.4 to 38.6)	[9]	1	8

Human leukocyte antigen (HLA) alleles associated with hypersensitivity reactions and drug-induced liver injury (DILI) are presented. All but two DILI studies (one Japanese and one Indian) were conducted in individuals of Caucasian ancestry. The number of individuals whose peripheral mononuclear cells are stored in the HLA-typed archive (n = 385) and who are carriers of HLA alleles implicated in these reactions is shown. CI, confidence Interval; Hmz, homozygotes; Htz, heterozygotes; ND, not determined (DQA1 locus not genotyped in ENW cohort); SJS, Stevens Johnson syndrome; TEN, toxic epidermal necrolysis.

ISSN: 1756-994X