Background
Context: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors.
Purpose: To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.
Findings
Methods: Children aged ≥9 years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children’s completion of a nausea diary (min. 7 days) and the parents’ completion of the MTX intolerance severity score (MISS). The selected SNPs were: SLCO1B1 (rs4149056; rs4149081), SLCO1B3 (rs2117032), SLC19A1 (rs1051266), ABCC2 (rs2273697; rs3740066; rs717620), ABCB1 (rs2032582; rs1045642), MTHFR (rs1801131, rs1801133), HTR3A (rs1062613; rs1985242; rs1176713) and HTR3B (rs1176744).
Results: Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3 years (IQR: 11.3-15.1). The median MTX dose was 9.7 mg/m2/week (IQR: 9.0-10.9). The median MTX treatment duration prior to enrolment was 340 days (IQR: 142-766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (MTHFR) (p= 0.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations.
Conclusion
Summary: MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR).
Implications: Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.
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Posted 05 Jan, 2021
On 16 Dec, 2020
On 16 Dec, 2020
On 16 Dec, 2020
On 17 Nov, 2020
Received 08 Nov, 2020
Received 08 Nov, 2020
Received 07 Nov, 2020
Received 07 Nov, 2020
On 28 Oct, 2020
On 27 Oct, 2020
On 27 Oct, 2020
On 26 Oct, 2020
Received 26 Oct, 2020
Received 25 Oct, 2020
Received 24 Oct, 2020
On 16 Oct, 2020
Received 16 Oct, 2020
On 13 Oct, 2020
On 13 Oct, 2020
Invitations sent on 12 Oct, 2020
On 12 Oct, 2020
On 17 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
On 14 Aug, 2020
Posted 05 Jan, 2021
On 16 Dec, 2020
On 16 Dec, 2020
On 16 Dec, 2020
On 17 Nov, 2020
Received 08 Nov, 2020
Received 08 Nov, 2020
Received 07 Nov, 2020
Received 07 Nov, 2020
On 28 Oct, 2020
On 27 Oct, 2020
On 27 Oct, 2020
On 26 Oct, 2020
Received 26 Oct, 2020
Received 25 Oct, 2020
Received 24 Oct, 2020
On 16 Oct, 2020
Received 16 Oct, 2020
On 13 Oct, 2020
On 13 Oct, 2020
Invitations sent on 12 Oct, 2020
On 12 Oct, 2020
On 17 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
On 14 Aug, 2020
Background
Context: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors.
Purpose: To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.
Findings
Methods: Children aged ≥9 years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children’s completion of a nausea diary (min. 7 days) and the parents’ completion of the MTX intolerance severity score (MISS). The selected SNPs were: SLCO1B1 (rs4149056; rs4149081), SLCO1B3 (rs2117032), SLC19A1 (rs1051266), ABCC2 (rs2273697; rs3740066; rs717620), ABCB1 (rs2032582; rs1045642), MTHFR (rs1801131, rs1801133), HTR3A (rs1062613; rs1985242; rs1176713) and HTR3B (rs1176744).
Results: Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3 years (IQR: 11.3-15.1). The median MTX dose was 9.7 mg/m2/week (IQR: 9.0-10.9). The median MTX treatment duration prior to enrolment was 340 days (IQR: 142-766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (MTHFR) (p= 0.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations.
Conclusion
Summary: MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR).
Implications: Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.
Figure 1
Figure 2
Figure 3
Figure 4
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