Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer
Aim: to analyze the role of nucleotide sequence variants (NSVs) of ABCG5 and ABCG8 genes in gallstone disease (GSD) and gallbladder cancer (GBC).Key points. ABCG5 and ABCG8 are key sterol efflux transporters that regulate hepatic secretion and intestinal absorption of cholesterol. ABCG5/G8 is the hu...
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Gastro LLC
2025-06-01
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| Series: | Российский журнал гастроэнтерологии, гепатологии, колопроктологии |
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| Online Access: | https://www.gastro-j.ru/jour/article/view/951 |
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| author | I. N. Grigor’eva T. E. Notova D. L. Nepomnyashchikh |
| author_facet | I. N. Grigor’eva T. E. Notova D. L. Nepomnyashchikh |
| author_sort | I. N. Grigor’eva |
| collection | DOAJ |
| description | Aim: to analyze the role of nucleotide sequence variants (NSVs) of ABCG5 and ABCG8 genes in gallstone disease (GSD) and gallbladder cancer (GBC).Key points. ABCG5 and ABCG8 are key sterol efflux transporters that regulate hepatic secretion and intestinal absorption of cholesterol. ABCG5/G8 is the human LITH9 gallstone gene. One of the major genetic risk factors for GSD rs11887534 (D19H) ABCG8, as a ‘gain-of-function’ NSV, increases the activity of this transporter by 3.2 times, which leads to supersaturation of bile with cholesterol and an increased risk of GSD. On average, rs11887534 increasesthe risk of GSD in children by 4 times, in adults — by 2 times, which has been proven in population, genome-wide studies and meta-analyses worldwide. The presence of the H allele D19H (rs11887534) is associated with a two-fold risk of recurrence of GSD after cholecystectomy. The results of the studies of the associations of GSD with other NSVs of ABCG8 (T400K, A632V, M429V, C54Y) and ABCG5 (E604Q, R50C) genes are contradictory.In population studies, rs11887534 was associated with a 4-fold increase in the risk of GBC, and the risk is more prominent (4.9 times) in patients with GBC and gallstones. We found no studies of the NSVs of the ABCG5 and ABCG8 genes in biliary pathology in Russia.Conclusion. Most studies confirm the role of the rs11887534 ABCG8 gene as a predictor of GSD and GBC; however, replicating studies of NSVs of ABCG5 and ABCG8 genes in biliary pathology in Russia are needed. |
| format | Article |
| id | doaj-art-e24f951b365446af95aa2d15b25e7d8f |
| institution | Kabale University |
| issn | 1382-4376 2658-6673 |
| language | Russian |
| publishDate | 2025-06-01 |
| publisher | Gastro LLC |
| record_format | Article |
| series | Российский журнал гастроэнтерологии, гепатологии, колопроктологии |
| spelling | doaj-art-e24f951b365446af95aa2d15b25e7d8f2025-08-20T04:02:42ZrusGastro LLCРоссийский журнал гастроэнтерологии, гепатологии, колопроктологии1382-43762658-66732025-06-01352374410.22416/1382-4376-2025-35-2-37-441180Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder CancerI. N. Grigor’eva0T. E. Notova1D. L. Nepomnyashchikh2Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesState Novosibirsk Regional Clinical HospitalNovosibirsk State Medical UniversityAim: to analyze the role of nucleotide sequence variants (NSVs) of ABCG5 and ABCG8 genes in gallstone disease (GSD) and gallbladder cancer (GBC).Key points. ABCG5 and ABCG8 are key sterol efflux transporters that regulate hepatic secretion and intestinal absorption of cholesterol. ABCG5/G8 is the human LITH9 gallstone gene. One of the major genetic risk factors for GSD rs11887534 (D19H) ABCG8, as a ‘gain-of-function’ NSV, increases the activity of this transporter by 3.2 times, which leads to supersaturation of bile with cholesterol and an increased risk of GSD. On average, rs11887534 increasesthe risk of GSD in children by 4 times, in adults — by 2 times, which has been proven in population, genome-wide studies and meta-analyses worldwide. The presence of the H allele D19H (rs11887534) is associated with a two-fold risk of recurrence of GSD after cholecystectomy. The results of the studies of the associations of GSD with other NSVs of ABCG8 (T400K, A632V, M429V, C54Y) and ABCG5 (E604Q, R50C) genes are contradictory.In population studies, rs11887534 was associated with a 4-fold increase in the risk of GBC, and the risk is more prominent (4.9 times) in patients with GBC and gallstones. We found no studies of the NSVs of the ABCG5 and ABCG8 genes in biliary pathology in Russia.Conclusion. Most studies confirm the role of the rs11887534 ABCG8 gene as a predictor of GSD and GBC; however, replicating studies of NSVs of ABCG5 and ABCG8 genes in biliary pathology in Russia are needed.https://www.gastro-j.ru/jour/article/view/951gallstone disease,gallbladder cancensv<i>abcg5</i><i>abcg8</i>rs11887534 |
| spellingShingle | I. N. Grigor’eva T. E. Notova D. L. Nepomnyashchikh Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer Российский журнал гастроэнтерологии, гепатологии, колопроктологии gallstone disease, gallbladder cance nsv <i>abcg5</i> <i>abcg8</i> rs11887534 |
| title | Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer |
| title_full | Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer |
| title_fullStr | Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer |
| title_full_unstemmed | Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer |
| title_short | Association of <i>ABCG5</i> and <i>ABCG8</i> Polymorphisms with Gallstone Disease and Gallbladder Cancer |
| title_sort | association of i abcg5 i and i abcg8 i polymorphisms with gallstone disease and gallbladder cancer |
| topic | gallstone disease, gallbladder cance nsv <i>abcg5</i> <i>abcg8</i> rs11887534 |
| url | https://www.gastro-j.ru/jour/article/view/951 |
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