Apolipoprotein E polymorphism and lithogenic factors in gallbladder bile

Abstract

In comparison to the non apo E4 patients the apo E4 group showed a trend to elevated biliary cholesterol whereas crystal observation time, cholesterol saturation index, crystal mass, number of gallstones, cholesterol content of gallstones and total protein and mucin were not different. These findings do not suggest an association of the apo E isoform and the formation of cholesterol gallstones

Genetic analysis of cholesterol gallstone formation: Searching for Lith (gallstone) genes

“…Some studies have reported that certain polymorphisms of the apolipoprotein (APO) E and B genes and the cholesterol ester transfer protein, all of which are involved in carrying cholesterol in the plasma, were associated with gallstones [53][54][55][56][57][58][59]. APOE polymorphism is the most extensively studied polymorphism in gallstone patients; however, controversial results have been reported concerning the protective role of the ε 4 allele against gallstones [53][54][55][56]. Kesaniemi et al [57] reported that the ε 2 allele appears to act as a protecting factor against gallstones.…”

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations

“…A second casecontrol study performed in Spain (29) indicated that the apoE4 isoform occurs more frequently in patients with gallstones compared with stone-free subjects, but these differences were significant only in women. In contrast to the Finnish study, other authors did not detect an association of apoE4 with an increased cholesterol content of gallstones or rapid cholesterol crystal formation (29,34,35). On the other hand, higher stone recurrence rates after extracorporeal shock-wave lithotripsy has been described in apoE4 carriers (54).…”

“…The apoE2 isoform, by contrast, was found less frequently in Finnish women with gallstones than in controls (30). However, other studies have not yielded consistent association findings (31)(32)(33)(34)(35). The association between gallstones and APOE could be attributable to higher intestinal cholesterol absorption (36,37) and increased hepatic cholesterol uptake in apoE4 carriers (21,25).…”

“…Increased hepatic cholesterol uptake via chylomicrons represses LDL receptors (38) and HMG-CoA reductase (38). This would explain the reduction of fecal bile salt excretion observed in apoE4 carriers (35) and lead to a decreased bile salt-cholesterol ratio in bile, although no significant difference in cholesterol saturation of gallbladder bile from patients with different apoE isoforms has been reported (28,32,38,39). Because holo-apoE is present in bile, it might alternatively, similar to apoA-I and apoA-II, have a role in the destabilization of bile and the modulation of cholesterol crystallization and stone growth.…”

Investigation of the Lith1 candidate genes ABCB11 and LXRA in human gallstone disease

“…An association of pigment gallstones with a promoter variation in the UDPglucuronosyltransferase 1A1 (UGT1A1) gene has been reported in patients with chronic hemolytic disorders 21,22 and cystic fibrosis. 23 Investigations of the 7-alpha-hydroxylase and apolipoproteins A and B in 105 to 210 patients [24][25][26][27] and apolipoprotein E in 37 to 169 patients 28,29 did not yield replicated association findings. A recent genome-wide linkage scan in Mexican Americans identified significant linkage (LOD 3.7) of gallstone susceptibility to chromosome 1p.…”