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Table 3 High-intensity interval training rheumatoid arthritis cohort #2: skeletal muscle canonical pathways associated with improvements in disease activity

From: Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis

Ingenuity canonical pathways – log
(p value)
Ratio (genes/total genes) Positively associated genes Negatively associated genes
Proline biosynthesis II 3.84 4/5 OAT,PYCR1,PYCR2,PYCR3  
Glycine cleavage complex 3.38 4/6 AMT,GCSH,GLDC,TBXT  
Purine biosynthesis II 3.14 5/11 ADSS1,IMPDH1,PAICS ADSS2,IMPDH2
Proline biosynthesis I 2.8 3/4 PYCR1,PYCR2,PYCR3  
nNOS signaling in skeletal muscle cells 2.63 9/40 CACNA1A,CACNA1C,CACNA1I,CACNA2D4, CACNB4,CACNG8,CHRNA1,RYR1 CACNB1
Sertoli cell-sertoli cell junction signaling 2.36 24/181 CLDN14,CLDN18,CLDN19,ITGA3,MAP2K3,MYO7A,PRKAG2,PRKG2,SYMPK,TJAP1,TUBB8 ACTC1,LK,MAP3K6,MAPK9,MRAS,NECTIN1, RASD1,RRAS,SORBS1,SPTBN1,TUBA1A,TUBB2A, TUBB2B
L-DOPA degradation 2.25 2/2 COMT,LRTOMT  
VDR/RXR activation 1.94 12/77 HOXA10,HSD17B2,IGFBP3,IGFBP5,KLK6,NCOR2, RXRB,SEMA3B,SULT2A1,WT1 CASR,TRPV6
Ethanol degradation II 1.88 6/27 ADH1C,AKR1A1,ALDH3A1,ALDH9A1 ACSS2,ALDH7A1
Estrogen receptor signaling 1.84 35/319 AGT,ATP5F1A,ATP5PB,BCL2,CACNA1A,CACNA1C,CTBP1,EGFR,ESR1,GNAO1,HIF1A,MED10,MED14, MED16,MED4, MED6, NCOR2,PLCB1,PRKAG2, TFAM,TYK2,VEGFC CTBP2,EGF,FOXO6,MMP19,MMP20,MMP21,MRAS,MYL1,MYL6,PLCB2, POLR2B,RASD1,RRAS
HIF1α signaling 1.84 24/200 APEX1,ARAF,BMP6,CAMK1D,HIF1A,HSPA4, HSPA6,LDHB,MAP2K3,MKNK2,MMP19,MMP20, SLC2A14,SLC2A3,VEGFC CCNG2,EGF,MDM2,MMP21,MRAS,PPP3R1,RAN,
RASD1,RRAS
Methylglyoxal degradation III 1.77 4/14 AKR1A1,DHRS11 AKR1C1/AKR1C2,AKR1C3
Estrogen-dependent breast cancer signaling 1.72 11/73 DHRS11,EGFR,ESR1,HSD17B11,HSD17B12, HSD17B2 AKR1C4,MRAS,RASD1,RRAS,TERT
Vitamin-C transport 1.6 5/23 NXN,SLC2A3,TXNRD3 AKR1C4,LRRC8A
2-KG dehydrogenase complex 1.52 2/4 DLST OGDH
Branched-chain α-keto acid dehydrogenase complex*# 1.52 2/4 BCKDHB,DBT  
Neuroprotective role of THOP1 in Alzheimer’s disease 1.49 14/109 AGT,APP,GNRH2,GZMA,KLK12,KLK6,PRKAG2, PRSS3,SERPINA3 FAP,HLA-B,PRSS23,ST14,YWHAE
Glycogen degradation II 1.36 3/11 AGL,PGM5 TYMP
  1. Results of ingenuity canonical pathways analyses, with pathways reaching significance at p > 0.05 included. Ratio refers to the number of differentially expressed skeletal muscle genes significantly associated (Spearman correlations, p < 0.05) with improvements in rheumatoid arthritis (RA) (RA) (n = 12 participants) disease activity score in 28 joints (DAS-28) following high-intensity interval training (HIIT) compared to the total number genes in that pathway. Subsequent significant pathways with at least 50% gene overlap from previous listed pathways are filtered from this table. Please see Supplementary Table 4 for full list of significant canonical pathways
  2. *#Pathway significantly associated in both the cross-sectional RA cohort #1 and changes with high-intensity interval training (HIIT) RA cohort #2 analyses