Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity.

Shaffer, E.A.; Small, Donald

doi:10.1172/jci108705

Cited by 320 publications

(137 citation statements)

References 43 publications

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“…4,18,45 Furthermore, the 19H allele has also been associated with higher serum levels of cholesterol precursors (cholestanol, lathosterol), 23 indicating increased cholesterol biosynthesis, as has been observed in obese gallstone patients. 46,47 These findings taken together suggest low intestinal cholesterol absorption and high compensatory cholesterol biosynthesis in carriers of the ABCG8 D19H variant, as hypothesized previously by Gylling et al 23 Of note, the up-regulated cholesterol biosynthesis in these subjects explains the greater efficacy of HMG-CoA reductase inhibitors such as atorvastatin therapy in 19H carriers. 28 In fact, statins are reported to decrease the cholesterol saturation index of duodenal bile and to dissolve gallstones in some patients 48 but not in gallstone patients in general.…”

Section: Discussionsupporting

confidence: 60%

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

et al. 2007

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Genomewide scans of inbred strains of mice have linked the genes encoding the hepatocanalicular cholesterol transporter ABCG5/G8 to gallstone formation. Five nonsynonymous coding single-nucleotide polymorphisms (SNPs) in the orthologous human genes are associated with differences in serum cholesterol and plant sterol levels. We now tested these ABCG5/G8 SNPs for linkage and association with gallstone susceptibility in humans. Prospectively, we collected data from 178 white individuals with gallbladder stones or history of cholecystectomy in 84 families and from 70 stone-free controls, as confirmed by abdominal ultrasound. We performed nonparametric linkage (NPL) analysis of affected sib pairs (ASPs) and association tests of cases and controls. In ASPs, gallstones were strongly linked to the D19H variant of the ABCG8 gene (NPL score ‫؍‬ 7.1; P ‫؍‬ 4.6 ؋ 10 ؊13 ). The risk of gallstones in carriers of the 19H allele was significantly increased in randomly selected cases from the ASP cohort compared to the stone-free controls (OR ‫؍‬ 3.018; P ‫؍‬ 0.017). Consistent with the mouse model, heterozygosity for the lithogenic ABCG8 allele was associated with gallstones in humans; 21.4% of gallstone patients carried the heterozygous D19H genotype, compared with 8.6% of controls (OR ‫؍‬ 2.954; P ‫؍‬ 0.026). Conclusion: The linkage and association studies identified the cholesterol transporter ABCG5/G8 as a genetic determinant of gallstone formation, or LITH gene, in humans. The function of this transporter and the results of the genetic study taken together indicate that in gallstone-susceptible carriers of the ABCG8 19H allele, cholesterol cholelithiasis is secondary to increased hepatobiliary cholesterol secretion. (HEPATOLOGY 2007;46:793-801.)

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Section: Discussionsupporting

confidence: 60%

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

et al. 2007

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“…We found significantly higher serum BA levels in patients with cholecystectomy compared to patients with the gall bladder in situ 5 years after surgery. This may, completely or partly, be attributable to increased cycling of the BA pool in the enterohepatic circulation due to lack of storage capacity [39,40].…”

Section: Discussionmentioning

confidence: 99%

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Risstad

Kristinsson

Fagerland

et al. 2017

Surgery for Obesity and Related Diseases

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(2017). Bile acid profiles over 5 years following gastric bypass and duodenal switch -Results from a randomized clinical trial. Surgery for obesity and related diseases. https://doi.org/10.1016/j.soard.2017.05.024Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…bile acids by others. 16 Therefore, samples obtained from normal individuals are required to give more represen-…”

Section: Discussionmentioning

confidence: 99%

The effect of mannitol and secretin on the biliary transport of urate in humans

et al. 1996

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No evidence is available on the transport of biliary biliary route) may be increased in certain pathological urate and the possible role of choleretic agents in the conditions such as uremia. 2,3 In addition, several facregulation of biliary urate elimination in humans. To tors such as extracellular fluid volume, urine flow rate, test this hypothesis we studied the following: (1) 45 cho-alcohol, food components, many medications (mainly lecystomized patients to determine urate levels in he-pyrazinamide and probenecid), and hormones alter patic bile and gallbladder bile, and (2) 13 cholecysto-urate kidney transport. 4 Assuming that the physiologimized patients fitted with T-tubes to determine the cal processes of bile secretion and urine excretion share effects of secretin injection (either 70 U of porcine secre-many similarities, biliary urate transport may be modi- urate comes mainly from secreted compound, the filof a significant increase in mean bile flow (P õ .001), whereas the mean biliary urate concentration signifi-tered urate representing a percentage of less than 10% cantly decreased (P õ .001) with a concomitant decrease of the excreted amount. 6 On the other hand, the biliary in the mean serum urate concentration (P õ .02). Manni-transport of urate has not, to our knowledge, been pretol also induced a significant increase in the mean urate viously investigated. In view of the fact that extrarenal clearance (P õ .002) because of a significant increase in urate elimination (including the biliary elimination the mean biliary urate concentration (P õ .01) with a route) may be important in some of the previously menconcomitant decrease in the mean serum urate concen-tioned pathological conditions, we sought to investigate tration (P õ .01) and without changes in the mean bile the biliary urate clearance (1)

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Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity.

Cited by 320 publications

References 43 publications

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

The effect of mannitol and secretin on the biliary transport of urate in humans

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