Apolipoprotein B‐100 gene <i>Xba I</i> polymorphism and cholesterol gallstone disease

Han, Tao; Jiang, Zhaoyan; Suo, Guangjun; Zhang, Sheng-Dao

doi:10.1034/j.1399-0004.2000.570410.x

Cited by 51 publications

(41 citation statements)

References 32 publications

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“…[9][10][11][12] However, the metabolic abnormalities underlying the supersaturation of bile and the formation of cholesterol gallstones induced by APO-B expression and/or polymorphisms are not yet fully understood. Thus the use of Apob 48/48 and Apob 100/100 mice should help to elucidate whether their expression levels are critical for cholesterol gallstone formation and to dissect the potential pathophysiological roles of each APO-B subtype, APO-B48 and APO-B100, in the formation of gallstones.…”

Section: Discussionmentioning

confidence: 99%

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Reduced Susceptibility to Cholesterol Gallstone Formation in Mice That Do Not Produce Apolipoprotein B48 in the Intestine *

Wang

2005

Hepatology

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It has been found that polymorphisms in the apolipoprotein (APO)-B gene are associated with cholesterol gallstones in humans. We hypothesized that APO-B plays a major regulatory role in the response of biliary cholesterol secretion to high dietary cholesterol and contributes to cholesterol gallstone formation. In the present study, we investigated whether lack of expression of intestinal Apob48 or Apob100 reduces susceptibility to cholesterol gallstones by decreasing intestinal absorption and biliary secretion of cholesterol in male mice homozygous for an "APO-B48 only" allele (Apob 48/48 ), an "APO-B100 only" allele (Apob 100/100 ), or a wild-type APO-B allele (Apob ؉/؉ ) before and during an 8-week lithogenic diet. We found that cholesterol absorption was significantly decreased as a result of the APO-B48 deficiency in Apob 100/100 mice compared with wild-type and Apob 48/48 mice, regardless of whether chow or the lithogenic diet was administered. Consequently, hepatic cholesterol synthesis was significantly increased in Apob 100/ 100 mice compared with wild-type and Apob 48/48 mice. On chow, the APO-B100 deficiency in S tudies in humans and inbred mice have demonstrated that a complex genetic basis determines the individual and strain predisposition to develop cholesterol gallstones in response to environmental factors. 1 The primary pathophysiological defect involved in cholesterol gallstone formation is increased biliary secretion of cholesterol from the liver, which produces bile supersaturated with cholesterol. 2 Subsequently, biliary cholesterol precipitates as "anhydrous" and monohydrate crystals, which grow and agglomerate toward the formation of macroscopic stones in the gallbladder. Biliary cholesterol is mostly derived from circulating lipoproteins, which originate from the hepatic uptake of plasma high-density lipoprotein (HDL) and chylomicron remnants. [3][4][5][6][7][8] Thus, the potential interrelationship between lipoprotein metabolism-related genes and cholesterol gallstones requires further investigation. In particular, it has been found that polymorphisms in the apolipoprotein (APO)-B gene are associated with cholesterol gallstones in humans. 9-12 Therefore, we hypothesized that APO-B plays a major regulatory role in the response of biliary cholesterol secretion to high dietary cholesterol and contributes to the formation of cholesterol gallstones. APO-B has two different isoforms, APO-B48 and APO-B100, and plays a particularly critical role in the Abbreviations: APO, apolipoprotein; HDL, VLDL, LDL, mRNA, messenger RNA.

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Section: Discussionmentioning

confidence: 99%

“…In particular, it has been found that polymorphisms in the apolipoprotein (APO)-B gene are associated with cholesterol gallstones in humans. [9][10][11][12] Therefore, we hypothesized that APO-B plays a major regulatory role in the response of biliary cholesterol secretion to high dietary cholesterol and contributes to the formation of cholesterol gallstones.…”

mentioning

confidence: 99%

Reduced Susceptibility to Cholesterol Gallstone Formation in Mice That Do Not Produce Apolipoprotein B48 in the Intestine *

Wang

2005

Hepatology

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“…Although not associated previously with PE or CHT, an APOB polymorphism (Thr2488Thr, CϾT) was added to the list of candidate polymorphisms for both diseases. The rationale for testing this polymorphism for PE consists in its association with serum level of LDL and apolipoprotein B 41,42 and the link between preeclampsia and increased serum concentration of small dense LDL. 4 For chronic essential hypertension, the rationale was based on the fact that an association of another polymorphism of APOB with blood pressure was reported previously.…”

Section: Association Study Of Candidate Genesmentioning

confidence: 99%

Implication of an AGT Haplotype in a Multigene Association Study With Pregnancy Hypertension

et al. 2004

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Abstract-Several association studies of candidate genes for preeclampsia and essential hypertension have led to discordant results, partly because of small sample sizes. Using a large population-based sample of pregnant women, we conducted an association study of 10 polymorphisms in 9 genes and aimed (1) to validate 10 published associations with preeclampsia or essential hypertension, (2) to investigate candidate polymorphisms previously associated with preeclampsia for association with essential hypertension and similarly with polymorphisms previously associated with essential hypertension. From a prospective sample of 3391 nulliparous French Canadian pregnant women, we identified 180 cases of preeclampsia, 203 cases of essential hypertension that were matched with normotensive control subjects (nϭ310 and 357, respectively). Polymorphisms were genotyped by allele-specific PCR. Among our candidate polymorphisms, the Met allele of Thr174Met of AGT was associated with preeclampsia (Pϭ0.0033). Haplotype analysis revealed that the A-Met-Thr (G1035A-Thr174Met-Met235Thr) haplotype was associated with a 2.1-fold increased risk of preeclampsia (95% CI, 1.4 to 3.4; Pϭ0.0008). In conclusion, we observed a strong association between a specific AGT haplotype and preeclampsia in our population, without replicating previous published associations with either preeclampsia or essential hypertension. Our data support a role for AGT in genetic susceptibility to preeclampsia.

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“…APOB XbaI polymorphism analysis was done as described previously (12). Allele was designated X + when restriction site for XbaI was present.…”

Section: Genotypingmentioning

confidence: 99%

“…This polymorphism of APOB has also been studied in gallstone patients. Han et al (12) found X + allele to be significantly higher, but in the Finnish population this polymorphism was not found to be associated with the gallstone disease (11,12).…”

Section: Introductionmentioning

confidence: 99%