ABCMdb

PMID: 21538282

Krawczyk M, Wang DQ, Portincasa P, Lammert F
Dissecting the genetic heterogeneity of gallbladder stone formation.
Semin Liver Dis. 2011 May;31(2):157-72. Epub 2011 May 2., [PubMed]

Sentences

No. Mutations Sentence Comment

56 ABCG8 p.Asp19His The most informative SNP proved to be the coding variant p.D19H of the heterodimeric cholesterol transporter ABCG8. Login to comment 57 ABCG8 p.Asp19His The odds ratio of developing gallstones among heterozygous carriers of the p.D19H risk variant was 2.2 (95% CI, 1.8-2.6; P ¼ 1.4 Â 10 À14 ). Login to comment 60 ABCG8 p.Asp19His ABCG8 p.Asp19His The NPL score demonstrated significant (NPL score ¼ 7.1, P ¼ 4.6 Â 10À13 ) linkage between the ABCG8 p.D19H variant and gallstone disease.69 As shown in detail in Table 2, the association between the ABCG8 variant and gallstones has subsequently been replicated in other cohorts, including the Swedish Twin Registry.70-73 The most recent study from Denmark72 illustrated that the absolute 10-year risk for symptomatic gallstone disease increases from men to women, with increasing age, with increasing BMI, and by p.D19H genotype (Fig. 3). Login to comment 61 ABCG8 p.Asp19His Of note, the orthologous murine genes encoding the cholesterol transporter (Abcg5/g8) were previously also identified as lithogenic genes (Lith9) in inbred Figure 3 Absolute 10-year risk of gallstone disease as a function of gender, age, body mass index (BMI) and ABCG8 p.D19H risk genotype (from72 with permission John Wiley and Sons, Inc.). Login to comment 62 ABCG8 p.Asp19His Table 2 Studies Investigating the Role of ABCG8 p.D19H in Gallstone Disease Year Population N Odds Ratio Risk Allele Frequency % Buch et al68 2007 Germany 1.832 2.2, 7.1** 5.0 Chile 167 1.9 7.0 Gru¨nhage et al69 2007 Romania 178 3.0 8.5 Kuo et al71 2008 China 74 3.5 1.4 Katsika et al70 2010 Sweden 341 2.5 6.8 Siddapuram et al73 2010 India 226 2.3 8.2 Stender et al72 2011 Denmark 3.124 1.9*, 3.3** 6.4 OR values are given for the carriership of the 19H risk allele, except for *carriers of the heterozygous genotype DH, and **homozygous carriers of the HH genotype. Login to comment 84 ABCG8 p.Asp19His In the future, common risk factors conferring moderate gallstone risk such as ABCG8 p.D19H might be genotyped in individual patients to stratify their gallstone risk (see below), but these tests are currently only used in the setting of diagnostic or epidemiologic studies. Login to comment