Gallbladder Disease in Pima Indians

Sampliner, Richard E.; Bennett, Peter H.; Comess, Leonard J.; Rose, F. A.; Burch, Thomas A.

doi:10.1056/nejm197012172832502

Cited by 341 publications

(29 citation statements)

References 14 publications

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“…Indian women without stones are particularly prone to development of the disease (6). Among Indian men and Caucasian women, gallstones occur less often than in Indian women, but they are found more frequently than in Caucasian men (6,(28)(29)(30). Therefore, in comparing hepatic secretion rates, the "normal" or ideal patterns of lipid secretion may not have been adequately defined.…”

Section: Discussionmentioning

confidence: 99%

“…This method estimates hourly rates of hepatic secretion of cholesterol, bile acids, and phospholipids in pa-tients with an intact enterohepatic circulation. We have applied this technique to the study of American Indian women who are particularly prone to development of cholesterol gallstones (6), and the results were compared with those obtained from three groups of subjects without stones-Indian men, Indian women, and Caucasian women. The findings showed that Indian women with stones have two abnormalities leading to the production of lithogenic bile; not only were bile acids secreted at a reduced rate by the liver, as might have been predicted from the studies of Vlahcevic and associates (3,4), but also, outputs of cholesterol were increased.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Lithogenic Bile Formation in American Indian Women with Cholesterol Gallstones

Grundy¹,

Metzger²,

Adler³

1972

J. Clin. Invest.

220

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A B S T R A C T Hepatic secretions of biliary lipids were estimated in 43 patients with and without cholesterol gallstones. Studies were carried out by a marker dilution technique employing duodenal intubation with a threelumen tube. Hourly secretion rates of cholesterol, bile acids, and phospholipids were determined during constant infusion with liquid formula.In 17 American Indian women with gallstones, hourly outputs of biliary bile acids were significantly less than those in 7 Indian men and 12 Caucasian women without gallstones. These findings suggest that a decreased hepatic secretion of bile acids contributes significantly to the production of a lithogenic bile in Indian women. However, in Indian women witlh gallstones, secretion of biliary cholesterol was also significantly increased, as compared with Caucasian women without stones. Therefore, lithogenic bile in Indian women was, in most cases. due to a combined decrease in bile acid output and increase in cholesterol secretion.In an attempt to determine the mechanisms for these abnormalities, cholesterol balance studies were done in Indian women with gallstones and normal Indian men. Balance data were compared with results reported previously in non-Indian patients studied by the same techniques, and in general, Indian women showed a slight increase in fecal excretion of bile acids. Since bile acids in the enterohepatic circulation were

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of Lithogenic Bile Formation in American Indian Women with Cholesterol Gallstones

Grundy¹,

Metzger²,

Adler³

1972

J. Clin. Invest.

220

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“…But later, in 1970 new posi tive cases were identified in the same population after oral cholecystograms had been performed in subjects who, in the previous study, had been excluded due to a negative history of gallstone disease. Analysis of the new, updated data showed that pregnancy was not a risk factor [ 13],…”

Section: Epidem Iologymentioning

confidence: 99%

Gallstone Disease in Pregnancy: Mere Coincidence or Physiologic Response?

Watemberg¹,

Avrahami²,

Landau³

et al. 1995

Dig Surg

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Albeit there have been numerous reports, but it has still not been completely clarified what the exact role (if any) of pregnancy is in the development of gallstone disease, or its influence in previously existing silent disease. Controversy remains, but a direct relation seems to exist between the number of pregnancies and the appearance of gallstones or sludge, mainly in young mothers. However, in many instances there has been a regression or disappearance of sludge, or even stones after delivery. Physiologically, pregnancy also affects the bile and the gallbladder (structurally and mechanically), probably rendering this combination of effects very lithogenic. In this review, the world literature is discussed and conclusions, as much as data permit, are reached regarding epidemiology, physiology, diagnosis and management of gallstone disease during pregnancy.

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“…Gallstone disease can be familial (6-11), and the bile from healthy sisters of female gallstone patients is more lithogenic than controls (11,12). In certain native populations of North and South America, a high percentage of adults develop cholesterol gallstones, suggesting common genetic factors (13,14).In previous studies, high fat plus high cholesterol diets produced atherosclerosis and gallstones in some strains of mice (15). In this report, we survey common inbred strains of mice for susceptibility to cholelithiasis and demonstrate that at least two genes determine the difference in gallstone susceptibility between strains AKR and C57L.…”

mentioning

confidence: 99%

“…Gallstone disease can be familial (6)(7)(8)(9)(10)(11), and the bile from healthy sisters of female gallstone patients is more lithogenic than controls (11,12). In certain native populations of North and South America, a high percentage of adults develop cholesterol gallstones, suggesting common genetic factors (13,14).…”

mentioning

confidence: 99%

Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice.

Khanuja

Cheah

Hunt

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

187

170

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The prevalence of cholesterol gallstones differs among inbred strains of mice fed a diet containing 15% (wt/wt) dairy fat, 1% (wt/wt) cholesterol, and 0.5% (wt/wt) cholic acid. Strains C57L, SWR, and A were notable for a high prevalence of cholelithiasis; strains C57BL/6, C3H, and SJL had an intermediate prevalence; and strains SM, AKR, and DBA/2 exhibited no cholelithiasis after consuming the diet for 18 weeks. Genetic analysis of the difference in gallstone prevalence rates between strains AKR and C57L was carried out by using the AKXL recombinant inbred strain set and (AKR x C57L)F1 x AKR backcross mice. Susceptibility to gallstone formation was found to be a dominant trait determined by at least two genes. A major gene, named Lithl, mapped to mouse chromosome 2. When examined after 6 weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.88) was downregulated as expected in the gallstone-resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L and SWR, the gallstone-susceptible strains. This suggests that regulation of the rate-limiting enzyme in cholesterol biosynthesis may be pivotal in determining the occurrence and severity of cholesterol hypersecretion and hence lithogenicity of gallbladder bile. These studies indicate that genetic factors are critical in determining gallstone formation and that the genetic resources of the mouse model may permit these factors to be identified.Both atherosclerosis and cholelithiasis result from excess cholesterol; in the one case cholesterol is deposited in arterial walls, and in the other case cholesterol precipitates in the gallbladder. Both diseases are prevalent in cultures consuming a Western diet, and both can be induced in animal models by a diet high in cholesterol (1,2). In Western cultures, heart disease is the major cause of death, and gallstone disease is present in 10-40% of individuals over the age of 60 (3).Genetic factors apparently play an important role in the development of cholesterol gallstone disease. Among studies of gallstone formation in animals, Alexander and Portman (4) demonstrated that C57BL/6 mice are susceptible to cholelithiasis, but CBA mice are resistant. In both strains bile was supersaturated with cholesterol but not to the same degree (4). Fujihara et al. (5) reported that the prevalence of gallstones varied from 0% to 100% among six strains of laboratory mice.Evidence for the importance of genetic factors in human cholelithiasis is limited. Gallstone disease can be familial (6-11), and the bile from healthy sisters of female gallstone patients is more lithogenic than controls (11,12). In certain native populations of North and South America, a high percentage of adults develop cholesterol gallstones, suggesting common genetic factors (13,14).In previous studies, high fat plus high cholesterol diets produced atherosclerosis and gallstones in some strains of mice (15). In this report, we survey common inbred strains of mice for susceptibility to cholelith...

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Gallbladder Disease in Pima Indians

Cited by 341 publications

References 14 publications

Mechanisms of Lithogenic Bile Formation in American Indian Women with Cholesterol Gallstones

Mechanisms of Lithogenic Bile Formation in American Indian Women with Cholesterol Gallstones

Gallstone Disease in Pregnancy: Mere Coincidence or Physiologic Response?

Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice.

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