{"title":"角蛋白 8 和 18 基因变异对酒精性肝病严重程度的影响。","authors":"Matthieu Tihy , Nathalie Lin-Marq , Thierry Berney , Laurent Spahr , Laura Rubbia-Brandt , Laure Elkrief","doi":"10.1016/j.labinv.2024.102133","DOIUrl":null,"url":null,"abstract":"<div><div>Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory–Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several <em>KRT8/18</em> genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of <em>KRT8/18</em> in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several <em>KRT8</em> (rs2070910, rs137898974, rs1065306) and <em>KRT18</em> (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several <em>KRT18</em> variants appeared associated with a poorer prognosis. These results highlight the possible role of <em>KRT18</em> variants in ALD.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"104 10","pages":"Article 102133"},"PeriodicalIF":5.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of Keratins 8 and 18 Genetic Variants on the Severity of Alcoholic Liver Disease\",\"authors\":\"Matthieu Tihy , Nathalie Lin-Marq , Thierry Berney , Laurent Spahr , Laura Rubbia-Brandt , Laure Elkrief\",\"doi\":\"10.1016/j.labinv.2024.102133\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory–Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several <em>KRT8/18</em> genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of <em>KRT8/18</em> in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several <em>KRT8</em> (rs2070910, rs137898974, rs1065306) and <em>KRT18</em> (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several <em>KRT18</em> variants appeared associated with a poorer prognosis. These results highlight the possible role of <em>KRT18</em> variants in ALD.</div></div>\",\"PeriodicalId\":17930,\"journal\":{\"name\":\"Laboratory Investigation\",\"volume\":\"104 10\",\"pages\":\"Article 102133\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Laboratory Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0023683724018117\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laboratory Investigation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0023683724018117","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Impact of Keratins 8 and 18 Genetic Variants on the Severity of Alcoholic Liver Disease
Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory–Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several KRT8/18 genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of KRT8/18 in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several KRT8 (rs2070910, rs137898974, rs1065306) and KRT18 (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several KRT18 variants appeared associated with a poorer prognosis. These results highlight the possible role of KRT18 variants in ALD.
期刊介绍：
Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.
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