Topic
TM6SF2
About: TM6SF2 is a research topic. Over the lifetime, 138 publications have been published within this topic receiving 10935 citations. The topic is also known as: transmembrane 6 superfamily member 2.
Papers
TL;DR: Variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. To identify genetic variants contributing to differences in hepatic fat content, we carried out a genome-wide association scan of nonsynonymous sequence variations (n = 9,229) in a population comprising Hispanic, African American and European American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels (P = 5.9 x 10(-10)) and with hepatic inflammation (P = 3.7 x 10(-4)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers. Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I) that was associated with lower hepatic fat content in African Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
3,222 citations
TL;DR: Exome-wide association study of liver fat content and adeno-associated virus–mediated short hairpin RNA knockdown of Tm6sf2 in mice indicate that TM6 SF2 activity is required for normal VLDL secretion and that impaired TM6SF2 function causally contributes to NAFLD.
Abstract: Helen Hobbs, Jonathan Cohen and colleagues identify a nonsynonymous variant in TM6SF2 associated with susceptibility to nonalcoholic fatty acid liver disease. They further show that knockdown of Tm6sf2 in mice results in increased liver triglyceride content and reduced very-low-density lipoprotein (VLDL) secretion, suggesting that impaired TM6SF2 function contributes causally to disease risk.
1,120 citations
TL;DR: Examining the strength of the effect of the I148M (rs738409 C/G) patatin‐like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations provided unequivocal evidence of rs738 409 as a strong modifier of the natural history of NAFLD in different populations around the world.
902 citations
TL;DR: A loss‐of‐function variant in HSD17B13 was associated with a reduced risk of chronic liver disease and of progression from steatosis to steatohepatitis.
Abstract: Background Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. Methods We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples. Results A splice variant (rs72613567:TA) in HSD17B13, encoding the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, was found to be associated with reduced levels of ALT (P=4.2×10−12) and AST (P=6.2×10−10). Among DiscovEHR study participants, this variant was found to be associated with a re...
688 citations
TL;DR: In patients with NAFLD, adiponutrin rs738409 C→G genotype, encoding for I148M, is associated with the severity of steatosis and fibrosis and the presence of nonalcoholic steatohepatitis.
648 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 15 |
| 2020 | 16 |
| 2019 | 24 |
| 2018 | 17 |
| 2017 | 14 |
| 2016 | 25 |