NAT2 Gene rs1041983 is Associated with Anti-Tuberculosis Drug Induced Hepatotoxicity Among Pediatric Tuberculosis in Bandung, Indonesia

Figures & data

Figure 1 Pediatric TB inclusion process.

Table 1 Characteristic of ADIH and without ADIH Pediatrics TB

	ADIH	Without ADIH
Sex, n
Male	11 (35%)	17 (55%)
Female	20 (65%)	14 (45%)
Age, Mean (SD)	8.6 (5) years	8.2 (6) years
TB Diagnosis (%)
Pulmonary TB	13 (42%)	10 (32%)
Extrapulmonary TB	18 (58%)	21 (68%)
Enzyme level, median (range)
AST	178 (43–2952) IU/L	51 (33–65) IU/L
ALT	144 (39–2135) IU/L	43 (21–55) IU/L
Bilirubin total	2.36 (0.30–27) mg/dL	0.54 (0–1) mg/dL
Bilirubin direct	1.8 (0.10–22) mg/dL	0.32 (0.01–0.61) mg/dL

Abbreviations: SD, standard deviation; ADIH, acute drug induced hepatotoxicity; without ADIH, without acute drug induced hepatotoxicity (treatment tolerant control), TB, tuberculosis; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

Table 2 Allelic Frequency Allele of ADIH and without ADIH

SNP ID Allele	Risk Allele*	ADIH n (%)	Without ADIH n (%)	OR (95% CI)	p-value
rs1041983					0.019
T	T	42 (67.7)	29 (46.8)	2.39 (1.15–4.96)
C		20 (32.3)	33 (53.2)
rs1799929					0.133
T	T	12 (19.4)	6 (9.7)	2.24 (0.78–6.41)
C		50 (80.6)	56 (90.3)
rs1799930					0.150
A	A	38 (61.3)	30 (48.4)	1.69 (0.83–3.45)
G		24 (38.7)	32 (51.6)
rs1799931					0.659
A	A	14 (22.6)	12 (19.4)	1.22 (0.51–2.89)
G		48 (77.4)	50 (80.6)

Note: *Defines with allele in higher frequency in individual with ADIH than in without ADIH (treatment tolerant control).

Abbreviations: SNP, single nucleotide polymorphism; ADIH, acute drug induced hepatotoxicity; without ADIH, without acute drug induced hepatotoxicity (treatment tolerant control); OR, odds ratio; CI, confident interval; T, allele T; C, allele C; A, allele A; G, allele G.

Table 3 SNPs-Based Genotype Association Tests in ADIH and without ADIH

SNP ID	Allele 1/2	Risk Allele*	ADIH (n=31)			Without ADIH (n=31)			p-value
			1/1 n (%)	½ n (%)	2/2 n (%)	1/1 n(%)	½ n (%)	2/2 n (%)
rs1041983	T/C	T	15 (48.4)	12 (38.7)	4 (12.9)	8 (25.8)	13 (41.9)	10 (32.3)	0.093
rs1799929	T/C	T	3 (9.7)	6 (19.4)	22 (71.0)	0 (0)	6 (19.4)	25 (80.6)	0.203
rs1799930	A/G	A	19 (61.3)	0 (0)	12 (38.7)	15 (48.4)	0 (0)	16 (51.6)	0.311
rs1799931	A/G	A	1 (3.2)	12 (38.7)	18 (58.1)	1 (3.2)	10 (32.3)	20 (64.5)	0.866

Note: *Defines with allele in higher frequency in individual with ADIH than in without ADIH (treatment tolerant control).

Abbreviations: SNP, single nucleotide polymorphism; ADIH, acute drug induced hepatotoxicity; without ADIH, without acute drug induced hepatotoxicity (treatment tolerant control); OR, odds ratio; CI, confident interval; T, allele T; C, allele C; A, allele A; G, allele G.