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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication
Open Access

Decreased Pregnane X Receptor Expression in Children with Active Crohn’s Disease

Valentina Shakhnovich, Carrie Vyhlidal, Craig Friesen, Amber Hildreth, Vivekanand Singh, James Daniel, Gregory L. Kearns and J. Steven Leeder
Drug Metabolism and Disposition July 2016, 44 (7) 1066-1069; DOI: https://doi.org/10.1124/dmd.115.068742
Valentina Shakhnovich
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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Carrie Vyhlidal
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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Craig Friesen
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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Amber Hildreth
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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Vivekanand Singh
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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James Daniel
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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Gregory L. Kearns
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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J. Steven Leeder
The Children’s Mercy Hospital, Kansas City, Missouri (V.S., C.V., C.F., V.S., J.D., J.S.L.) University of California San Diego, San Diego, California (A.H.); Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas (G.L.K.). Laboratory of origin: The Children’s Mercy Hospital
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    Fig. 1.

    Relative gene expression of PXR (A), VIL1 (B), and CYP3A4 (C) in the TI and the duodenum of children with Crohn’s disease (CD; n = 18) versus age- and sex-matched controls without IBD (n = 12). Mean differences in relative gene expression (triplicate determinations of molecule number per sample, normalized to GAPDH, and log2-transformed) were compared between the TI and the duodenum in the same children, using a two-tailed paired Student’s t test (α = 0.05).

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    Fig. 2.

    Correlation relationships (Spearman’s correlation; α = 0.05) in relative gene expression (triplicate determinations of molecule number per sample, normalized to GAPDH, and log2-transformed) between (A) PXR and VIL1 across all tissue samples (n = 30; r = 0.78, P = 0.01); (B) PXR and IL8 in the TI of CD (r = –0.45, P = 0.06) and controls (r = 0.18, P = 0.6), (C) VIL1 and IL8 in the TI of CD (r = –0.44, P = 0.07) and controls (r = 0.27, P = 0.4), and (D) CYP3A4 and IL8 in the TI of CD (r = –0.68, P < 0.01) and controls (r = 0.21, P = 0.5). Crohn’s disease (CD) tissue denoted by cross (n = 18), control tissue by circle (n = 12).

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    • Supplemental Data -

      Supplementary Table 1 - Spearman’s correlation (α < 0.05) for genes of interest expressed in small intestinal tissue, duodenum and terminal ileum (TI), from 30 children; 18 children with Crohn’s disease (CD) with active inflammation in the TI , and 12 age- and sex-matched Controls without intestinal inflammation.

      Supplementary Table 2 - Spearman’s correlation (α < 0.05) for IL8 (marker of inflammation) and genes of interest expressed in the terminal ileum (TI) from 30 children; 18 children with Crohn’s disease (CD) with active inflammation in the TI, and 12 age- and sex-matched Controls without intestinal inflammation.

      Supplementary Figure 1 - Correlation relationship in mRNA gene expression between PXR and CYP3A4, across all tissue samples in children with (cross) and without Crohn’s disease (open circle).

      Supplementary Figure 2 - Correlation relationship in mRNA gene expression between VIL1 and CYP3A4, across all tissue samples in children with and without Crohn’s disease. Crohn’s disease tissue (cross), control tissue (circle).

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Drug Metabolism and Disposition: 44 (7)
Drug Metabolism and Disposition
Vol. 44, Issue 7
1 Jul 2016
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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication

PXR Expression in Pediatric Crohn’s

Valentina Shakhnovich, Carrie Vyhlidal, Craig Friesen, Amber Hildreth, Vivekanand Singh, James Daniel, Gregory L. Kearns and J. Steven Leeder
Drug Metabolism and Disposition July 1, 2016, 44 (7) 1066-1069; DOI: https://doi.org/10.1124/dmd.115.068742

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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication

PXR Expression in Pediatric Crohn’s

Valentina Shakhnovich, Carrie Vyhlidal, Craig Friesen, Amber Hildreth, Vivekanand Singh, James Daniel, Gregory L. Kearns and J. Steven Leeder
Drug Metabolism and Disposition July 1, 2016, 44 (7) 1066-1069; DOI: https://doi.org/10.1124/dmd.115.068742
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