DO: 0060262;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p21 | {Gallbladder disease 4} | 611465 | 3 | ABCG8 | 605460 |
A number sign (#) is used with this entry because of evidence that susceptibility to gallbladder disease is conferred by variation in the ABCG8 gene (605460) on chromosome 2p21.
For a phenotypic description and a discussion of genetic heterogeneity of gallbladder disease (GBD), see GBD1 (600803).
In a genomewide association scan, Buch et al. (2007) identified a SNP (rs11887534) in the ABCG8 gene on chromosome 2p21 (D19H; 605460.0009) that was significantly associated with gallstones in 3 replication studies. A study in 1,105 additional affected individuals replicated a disease association of D19H (p = 4.1 x 10(-9), 1.1 x 10(-4) after Bonferroni correction). Additional significant replication was achieved in 728 Germans (P = 2.8 x 10(-7)). The overall odds ratio in the full German sample was 2.2 and 7.1 for heterozygous and homozygous H allele carriers, corresponding to a population risk of about 11%. The association was stronger in those with cholesterol gallstones, suggesting that ABCG8 his19 may be associated with increased efficiency of cholesterol transport into the bile lumen, causing cholesterol hypersaturation of bile and promoting the formation of gallstones.
Buch, S., Schafmayer, C., Volzke, H., Becker, C., Franke, A., von Eller-Eberstein, H., Kluck, C., Bassmann, I., Brosch, M., Lammert, F., Miquel, J. F., Nervi, F., and 17 others. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nature Genet. 39: 995-999, 2007. [PubMed: 17632509] [Full Text: https://doi.org/10.1038/ng2101]