ABCMdb

PMID: 20494111

Marschall HU, Katsika D, Rudling M, Einarsson C
The genetic background of gallstone formation: an update.
Biochem Biophys Res Commun. 2010 May 21;396(1):58-62., [PubMed]

Sentences

No. Mutations Sentence Comment

33 ABCG8 p.Asp19His The genome-wide association study of gallstone patients from Germany and Chile [12] and a linkage study in affected sib pairs from Germany and Romania [13] then identified the D19H variant of ABCG8, located on chromosome 2, as a susceptibility factor for human gallstone disease. Login to comment 36 ABCG8 p.Asp19His ABCG8 p.Asp19His The D19H variant was replicated as a susceptibility factor for gallstone diseases in China, where D19H increased the gallstone risk in patients younger than 50 years of age (OR, 12.4; 95% CI, 1.7-90) [14]. Login to comment 37 ABCG5 p.Gln604Glu In Chinese gallstone populations, also other non-synonymous polymorphisms, Q604E on the ABCG5 gene [14], and T400 K on the ABCG8 gene [15] were associated with increased risk (OR, 6.4; CI, 1.3-30.7 [14] and 2.3; CI, 1.12-4.76 [15], respectively) but only in male patients older than 50 years of age. Login to comment 38 ABCG8 p.Asp19His ABCG8 p.Asp19His We recently confirmed D19H as a risk factor for symptomatic gallstone disease (OR, 2.5; CI, 1.3-4.8) in 341 Swedish twins where 20.8% of gallstone cases carried at least one D19H allele as compared to 9.4% in stone-free controls [16]. Login to comment 39 ABCG5 p.Gln604Glu We also found a trend (p = 0.052) for a positive association with the Q604E variant of the ABCG5 gene in this particular Swedish population (OR, 1.5; CI, 1.00-2.16) [16]. Login to comment 40 ABCG8 p.Asp19His American and European carriers of the D19H variant were found to have decreased intestinal cholesterol absorption and increased hepatic synthesis of cholesterol [17,18], leading to lower total and LDL-cholesterol [18]. Login to comment 41 ABCG5 p.Gln604Glu ABCG8 p.Asp19His Lower total cholesterol and triglyceride levels were also found in another study in Caucasian gallstone siblings, in this case both for carriers of the ABCG5 Q604E or ABCG8 D19H variants [19]. Login to comment 42 ABCG8 p.Asp19His Consistent with upregulated cholesterol synthesis, D19H carriers had a significantly more effective reduction of LDL-cholesterol during treatment with statins, which might be of clinical relevance [20]. Login to comment 45 ABCG8 p.Asp19His Taken together, these findings support the assumption that D19H increases the ABCG5/G8 mediated transfer of cholesterol into bile, which conversely results in biliary cholesterol hypersaturation. Login to comment 46 ABCG8 p.Asp19His However, a recent study in healthy non-obese Chinese provided discordant data, i.e., a significant association of D19H gene polymorphism with elevated total and LDL-cholesterol [23], which might be attributed to different ethnic background and dietary habits. Login to comment 53 ABCG8 p.Asp19His We also recently identified a co-inheritance of a novel ABCB4 mutation (c.2960C>T) and the ABCG8 D19H variant in a Swedish monozygotic twin pair where both sisters suffered from juvenile onset gallstone disease, oral contraceptive and pregnancy aggravated cholestatic liver disease, and progressive liver fibrosis [31]. Login to comment