NAT2*6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

doi:10.3748/wjg.v13.i45.6003

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Dec 7, 2007 (publication date) through Aug 31, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Clinical Research

World J Gastroenterol. Dec 7, 2007; 13(45): 6003-6008
Published online Dec 7, 2007. doi: 10.3748/wjg.v13.i45.6003

Table 1 Characteristics of pulmonary TB patients included in the study

Characteristics	TB
Number of patients	100
Age range (yr)	22-94
Age (mean ± SD)	64.0 ± 17.4
Gender (male/female)	56/44
Body mass index (kg/m²)	20.3 ± 2.9

Table 2 Five Haplotypes composed of four SNPs in NAT2

Haplotype	SNP
Haplotype	C282T	C481T	G590A	G857A
NAT24*	-	-	-	-
NAT26A*	+	-	+	-
NAT27B*	+	-	-	+
NAT211*	-	+	-	-
NAT213*	+	-	-	-

Plus or minus symbols for C282T, C481T, G590A, and G857A indicate the presence or absence of SNPs.

Table 3 Clinical characteristics and laboratory data of TB patients with or without adverse effect

	Hepatotoxicity			Skin rash			Eosinophilia
Clinical data	Present	Absent	P	Present	Absent	P	Present	Absent	P
	(n = 18)	(n = 82)		(n = 25)	(n = 75)		(n = 34)	(n = 66)
Age (mean ± SD)	60.8 ± 17.7	64.7 ± 17.3	0.3942	63.6 ± 18.1	64.7 ± 17.3	0.9028	63.3 ± 19.5	64.4 ± 16.3	0.7598
Gender (M/F)	9/9	47/35	0.6081	12/13	44/31	0.3640	25/9	31/35	0.0186
Body mass index (kg/m²)	19.6 ± 2.3	20.5 ± 3.1	0.2721	19.8 ± 2.5	20.6 ± 3.1	0.2626	19.8 ± 2.9	20.6 ± 3.0	0.2684
Baseline values
ALT (IU/L)	18.0 ± 10.4	21.1 ± 16.6	0.4527	23.1 ± 25.8	19.7 ± 10.4	0.3392	25.9 ± 24.4	17.8 ± 6.8	0.6571
AST (IU/L)	29.1 ± 26.8	26.8 ± 23.3	0.7188	31.3 ± 39.2	25.9 ± 15.9	0.3268	35.4 ± 38.5	23.0 ± 7.8	0.4277
TB (mg/dL)	0.48 ± 0.19	0.64 ± 0.43	0.1115	0.61 ± 0.44	0.61 ± 0.39	0.9874	0.62 ± 0.44	0.61 ± 0.38	0.9490
Creatinine (mg/dL)	0.64 ± 0.13	0.88 ± 1.10	0.3482	0.72 ± 0.28	0.87 ± 1.13	0.5121	0.82 ± 0.47	0.84 ± 1.17	0.9092
Eosinophils (/μL)	105.1 ± 120.6	115.5 ± 121.8	0.7434	104.7 ± 93.7	116.6 ± 129.3	0.6750	141.3 ± 133.4	99.3 ± 112.6	0.1011
During TB chemotherapy
Peak ALT (IU/L)	316.2 ± 281.7	40.0 ± 19.5	< 0.0001	147.8 ± 281.7	61.6 ± 88.1	0.0245	129.6 ± 284.1	59.2 ± 75.4	0.3885
Peak AST (IU/L)	294.5 ± 353.6	36.7 ± 21.5	< 0.0001	139.7 ± 222.9	73.1 ± 128.9	0.1325	116.3 ± 175.9	76.0 ± 149.3	0.2107
Peak TB (mg/dL)	1.20 ± 1.16	0.74 ± 0.53	0.0101	0.78 ± 0.47	0.84 ± 0.77	0.7039	0.92 ± 0.89	0.77 ± 0.58	0.3241
Peak Creatinine (mg/L)	0.76 ± 0.13	0.96 ± 1.23	0.4742	0.81 ± 0.13	0.97 ± 1.28	0.5316	0.87 ± 0.31	0.96 ± 1.36	0.7098
Peak Eosinophils (/μL)	692.4 ± 929.1	461.1 ± 844.7	0.4538	668.4 ± 773.9	447.5 ± 885.1	0.0058	1028.1 ± 1327.9	232.1 ± 114.9	< 0.0001

Table 4 Distributions of NAT2-haplotypes in TB patients with and without adverse effect

	Hepatotoxicity					Skin rash					Eosinophilia
Haplotype	Present(%)	Absent(%)	OR	95% CI	P	Present(%)	Absent(%)	OR	95% CI	P	Present(%)	Absent(%)	OR	95% CI	P
NAT24*	16 (44.4)	120 (73.2)	0.265	0.129-0.546	< 0.001	34 (68.0)	102 (68.0)	1.00	0.503-1.987	1.000	45 (66.2)	91 (68.9)	0.880	0.472-1.642	0.688
NAT26A*	14 (38.9)	29 (17.7)	3.535	1.648-7.585	0.001	12 (24.0)	31 (20.7)	1.22	0.570-2.607	0.609	15 (22.0)	28 (21.2)	1.052	0.517-2.138	0.889
NAT27B*	6 (16.7)	15 (9.1)	2.235	0.818-6.104	0.117	4 (8.0)	17 (11.3)	0.70	0.226-2.170	0.537	8 (11.8)	13 (9.9)	1.227	0.482-3.124	0.667
Total number	36	164				50	150				68	132

Table 5 Distribution of NAT2-diplotypes in TB patients with and without adverse effect

	Hepatotoxicity					Skin rash					Eosinophilia
Diplotype	Present(%)	Absent(%)	OR	95% CI	P	Present(%)	Absent(%)	OR	95% CI	P	Present(%)	Absent(%)	OR	95% CI	P
NAT24/4	4 (22.2)	42 (51.2)	0.272	0.083-0.897	0.032	12 (48.0)	34 (45.3)	1.113	0.449-2.757	0.817	14 (41.2)	32 (48.5)	0.744	0.322-1.717	0.488
NAT24/6A	7 (38.9)	23 (28.1)	1.632	0.564-4.726	0.366	7 (28.0)	23 (30.7)	0.879	0.323-2.394	0.801	11 (32.4)	19 (28.9)	1.183	0.484-2.894	0.713
NAT24/7B	1 (5.6)	13 (15.9)	0.312	0.038-2.555	0.278	3 (12.0)	11 (14.7)	0.793	0.203-3.108	0.740	6 (17.6)	8 (12.1)	1.554	0.492-4.909	0.453
NAT26A/6A	2 (11.1)	2 (2.4)	5.000	0.655-38.152	0.121	2 (8.0)	2 (2.7)	3.174	0.423-23.812	0.261	1 (2.9)	3 (4.5)	0.636	0.064-6.360	0.700
NAT26A/7B	3 (16.6)	2 (2.4)	8.000	1.230-52.023	0.029	1 (4.0)	4 (5.3)	0.74	0.079-6.945	0.792	2 (5.9)	3 (4.5)	1.313	0.209-8.257	0.772
NAT27B/7B	1 (5.6)	0 (0)	-	-	-	0 (0)	1 (1.3)	-	-	-	0 (0)	1 (1.5)	-	-	-
Total number	18	82				25	75				34	66

Citation: Higuchi N, Tahara N, Yanagihara K, Fukushima K, Suyama N, Inoue Y, Miyazaki Y, Kobayashi T, Yoshiura KI, Niikawa N, Wen CY, Isomoto H, Shikuwa S, Omagari K, Mizuta Y, Kohno S, Tsukamoto K. NAT2*6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis. World J Gastroenterol 2007; 13(45): 6003-6008
URL: https://www.wjgnet.com/1007-9327/full/v13/i45/6003.htm
DOI: https://dx.doi.org/10.3748/wjg.v13.i45.6003