Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea

Banny S. Wong; Michael Camilleri; Suwebatu Odunsi-Shiyanbade; Irene Busciglio; Duane Burton; Paula J. Carlson; Sanna McKinzie; Alan R. Zinsmeister

doi:10.1007/s10620-012-2035-5

Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea

Banny S. Wong, Michael Camilleri, Suwebatu Odunsi-Shiyanbade, Irene Busciglio, Duane Burton, Paula J. Carlson, Sanna McKinzie, Alan R. Zinsmeister

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Background Protein products of klothoβ (KLB) and fibroblast growth factor receptor 4 (FGFR4) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of KLB and FGFR4 infuence colonic transit (CT) in diarrheapredominant irritable bowel syndrome (IBS-D). Aim The purpose of this study was to test the hypothesis that colesevelam's slowing effects on CT in IBS-D patients is infuenced by genetic variants in KLB and FGFR4. Methods We examined pharmacogenetic effects of KLB and FGFR4 coding variants (SNPs) on scintigraphic CT response to the BA sequestrant, colesevelam 1.875 g b.i.d. versus placebo (PLA) for 14 days in 24 female IBS-D patients. Results FGFR4 rs351855 and KLB rs497501 were associated with differential colesevelam effects on ascending colon (AC) half-emptying time (t _1/2, P = 0.046 and P = 0.085 respectively) and on overall CT at 24 h (geometric center, GC24: P = 0.073 and P = 0.042, respectively), with slower transit for rs351855 GA/AA (but not for GG) and rs497501 CA/AA (but not CC) genotypes. Conclusion FGFR4 rs351855 and KLB rs4975017 SNPs may identify a subset of IBS-D patients with beneficial response to colesevelam.

Original language	English (US)
Pages (from-to)	1222-1226
Number of pages	5
Journal	Digestive diseases and sciences
Volume	57
Issue number	5
DOIs	https://doi.org/10.1007/s10620-012-2035-5
State	Published - May 2012

Keywords

Bile acid
FGFR4
Klothoβ

ASJC Scopus subject areas

Physiology
Gastroenterology

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10.1007/s10620-012-2035-5

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@article{87725ef73b934ba2a5b74a61f9db2b22,

title = "Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea",

abstract = "Background Protein products of klothoβ (KLB) and fibroblast growth factor receptor 4 (FGFR4) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of KLB and FGFR4 infuence colonic transit (CT) in diarrheapredominant irritable bowel syndrome (IBS-D). Aim The purpose of this study was to test the hypothesis that colesevelam's slowing effects on CT in IBS-D patients is infuenced by genetic variants in KLB and FGFR4. Methods We examined pharmacogenetic effects of KLB and FGFR4 coding variants (SNPs) on scintigraphic CT response to the BA sequestrant, colesevelam 1.875 g b.i.d. versus placebo (PLA) for 14 days in 24 female IBS-D patients. Results FGFR4 rs351855 and KLB rs497501 were associated with differential colesevelam effects on ascending colon (AC) half-emptying time (t 1/2, P = 0.046 and P = 0.085 respectively) and on overall CT at 24 h (geometric center, GC24: P = 0.073 and P = 0.042, respectively), with slower transit for rs351855 GA/AA (but not for GG) and rs497501 CA/AA (but not CC) genotypes. Conclusion FGFR4 rs351855 and KLB rs4975017 SNPs may identify a subset of IBS-D patients with beneficial response to colesevelam.",

keywords = "Bile acid, FGFR4, Klothoβ",

author = "Wong, {Banny S.} and Michael Camilleri and Suwebatu Odunsi-Shiyanbade and Irene Busciglio and Duane Burton and Carlson, {Paula J.} and Sanna McKinzie and Zinsmeister, {Alan R.}",

note = "Funding Information: Acknowledgments We thank Mary Lempke, Pharm. D., research pharmacist, and Cindy Stanislav, secretary, for assistance. This work is funded by grant RO1-DK092179 from the National Institutes of Health to Dr. Camilleri and by Mayo Clinic CTSA grant (RR24150).",

year = "2012",

month = may,

doi = "10.1007/s10620-012-2035-5",

language = "English (US)",

volume = "57",

pages = "1222--1226",

journal = "Digestive Diseases and Sciences",

issn = "0163-2116",

publisher = "Springer New York",

number = "5",

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TY - JOUR

T1 - Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea

AU - Wong, Banny S.

AU - Camilleri, Michael

AU - Odunsi-Shiyanbade, Suwebatu

AU - Busciglio, Irene

AU - Burton, Duane

AU - Carlson, Paula J.

AU - McKinzie, Sanna

AU - Zinsmeister, Alan R.

N1 - Funding Information: Acknowledgments We thank Mary Lempke, Pharm. D., research pharmacist, and Cindy Stanislav, secretary, for assistance. This work is funded by grant RO1-DK092179 from the National Institutes of Health to Dr. Camilleri and by Mayo Clinic CTSA grant (RR24150).

PY - 2012/5

Y1 - 2012/5

N2 - Background Protein products of klothoβ (KLB) and fibroblast growth factor receptor 4 (FGFR4) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of KLB and FGFR4 infuence colonic transit (CT) in diarrheapredominant irritable bowel syndrome (IBS-D). Aim The purpose of this study was to test the hypothesis that colesevelam's slowing effects on CT in IBS-D patients is infuenced by genetic variants in KLB and FGFR4. Methods We examined pharmacogenetic effects of KLB and FGFR4 coding variants (SNPs) on scintigraphic CT response to the BA sequestrant, colesevelam 1.875 g b.i.d. versus placebo (PLA) for 14 days in 24 female IBS-D patients. Results FGFR4 rs351855 and KLB rs497501 were associated with differential colesevelam effects on ascending colon (AC) half-emptying time (t 1/2, P = 0.046 and P = 0.085 respectively) and on overall CT at 24 h (geometric center, GC24: P = 0.073 and P = 0.042, respectively), with slower transit for rs351855 GA/AA (but not for GG) and rs497501 CA/AA (but not CC) genotypes. Conclusion FGFR4 rs351855 and KLB rs4975017 SNPs may identify a subset of IBS-D patients with beneficial response to colesevelam.

AB - Background Protein products of klothoβ (KLB) and fibroblast growth factor receptor 4 (FGFR4) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of KLB and FGFR4 infuence colonic transit (CT) in diarrheapredominant irritable bowel syndrome (IBS-D). Aim The purpose of this study was to test the hypothesis that colesevelam's slowing effects on CT in IBS-D patients is infuenced by genetic variants in KLB and FGFR4. Methods We examined pharmacogenetic effects of KLB and FGFR4 coding variants (SNPs) on scintigraphic CT response to the BA sequestrant, colesevelam 1.875 g b.i.d. versus placebo (PLA) for 14 days in 24 female IBS-D patients. Results FGFR4 rs351855 and KLB rs497501 were associated with differential colesevelam effects on ascending colon (AC) half-emptying time (t 1/2, P = 0.046 and P = 0.085 respectively) and on overall CT at 24 h (geometric center, GC24: P = 0.073 and P = 0.042, respectively), with slower transit for rs351855 GA/AA (but not for GG) and rs497501 CA/AA (but not CC) genotypes. Conclusion FGFR4 rs351855 and KLB rs4975017 SNPs may identify a subset of IBS-D patients with beneficial response to colesevelam.

KW - Bile acid

KW - FGFR4

KW - Klothoβ

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U2 - 10.1007/s10620-012-2035-5

DO - 10.1007/s10620-012-2035-5

M3 - Article

C2 - 22271411

AN - SCOPUS:84863619771

SN - 0163-2116

VL - 57

SP - 1222

EP - 1226

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

IS - 5

ER -

Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea

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