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

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

  Gene SNP Alleles, Major > minor MTXintolerant1 Allel count MTXtolerant 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
G > A 3 2 0.96 (0.15–5.96) 0.96
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
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
  1. 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
  2. N = 118, due to missing SNP data for two patients and MISS data for one
  3. OR Odds Ratio
  4. 1The MTXintolerant 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 MTXtolerant (n = 46)
  5. 2SNP variant not available for one child
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