Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis

Table 3 Single nucleotide polymorphisms in association with the phenotype “MTX intolerance”

	Gene	SNP	Alleles, Major > minor	MTX_intolerant¹ Allel count	MTX_tolerant Allel count	OR (95% CI)	p	Chr.	Genomic position	Consequence
Hepatic	ABCC2	rs2273697	G > A	36	22	1.05 (0.61–1.80)	0.87	10	99,804,058	Missense
Efflux	ABCC2	rs3740066²	G > A	58	35	1.15 (0.64–2.07)	0.64	10	99,844,450	Missense
Transporter	ABCC2	rs717620	G > A	29	23	0.77 (0.42–1.41)	0.40	10	99,782,821	5’UTR variant
	ABCB1	rs2032582	G > T	61	34	1.28 (0.73–2.24)	0.39	7	87,531,302	Missense
	ABCB1	rs2032582	G > A	3	2	0.96 (0.15–5.96)	0.96	7	87,531,302	Missense
	ABCB1	rs1045642	T > C	62	42	0.88 (0.49–1.57)	0.67	7	87,509,329	Synonymous
Hepatic	SLCO1B1	rs4149056	T > C	25	13	1.28 (0.62–2.66)	0.51	12	21,178,615	Missense
Influx	SLCO1B1	rs4149081	G > A	27	15	1.19 (0.59–2.43)	0.62	12	21,225,087	Intron variant
Transporter	SLCO1B3	rs2117032	T > C	52	34	0.97 (0.57–1.64)	0.90	12	20,921,188	Down stream 3’UTR
Transporter	SLC19A1	rs1051266²	G > A	64	38	1.20 (0.67–2.13)	0.54	21	45,537,880	Missense
Nausea	HTR3A	rs1062613	C > T	20	20	0.55 (0.27–1.14)	0.11	11	113,975,284	5’UTR variant
Receptor	HTR3A	rs1985242	T > A	36	32	0.58 (0.31–1.09)	0.09	11	113,977,551	5’UTR variant
	HTR3A	rs1176713	T > C	27	22	0.74 (0.40–1.39)	0.35	11	113,989,703	Synonymous
	HTR3B	rs1176744	T > G	52	27	1.36 (0.78–2.54)	0.26	11	113,932,306	Missense
MTHFR	MTHFR	rs1801131²	A > C	44	34	0.77 (0.44–1.33)	0.35	1	11,794,419	Missense
Enzyme	MTHFR	rs1801133	C > T	49	21	1.77 (0.96–3.28)	0.07	1	11,796,321	Missense

The additive effect of the minor allele on parent-assessed MTX-induced nausea – the methotrexate intolerance severity score. Listed for every single nucleotide polymorphism (SNP) are the respective gene, the alleles, the relevant chromosome (Chr.), the genomic position, and the consequence of the SNP
N = 118, due to missing SNP data for two patients and MISS data for one
OR Odds Ratio
¹The MTX_intolerant subgroup: children with a total score of the Methotrexate Intolerance Severity Score (MISS) ≥6 and at least 1 point in the anticipatory and/or associative and/or behavioral symptoms (n = 72). Otherwise categorised as MTX_tolerant (n = 46)
²SNP variant not available for one child

ISSN: 1546-0096