Dataset Information

Trouble With Tribbles-1.

ABSTRACT: Genome-wide association studies (GWAS) have identified hundreds of genomic loci in humans that are significantly associated with plasma cholesterol, triglycerides, and coronary artery disease. Although some loci contain genes with known regulatory roles in lipid metabolism and atherosclerosis, the majority were being implicated for the first time. The 8q24 locus, containing the gene TRIB1 ( Tribbles-1), is the only novel GWAS locus that associates with all 4 plasma lipid traits and coronary artery disease, an observation that has spurred immense interest in this locus. Subsequent in vivo loss and gain of function studies confirmed that Trib1 plays a role in hepatic lipid metabolism, validating the initial genetic observation. Yet, many challenges remain in discerning the nature of the association between the TRIB1 locus and cardiometabolic phenotypes. Is TRIB1 the causal gene at the 8q24 locus and what is the functional consequence of the associated noncoding variation? Is the relationship between TRIB1 and the transcription factor C/EBP? (CCAAT/enhancer-binding protein alpha) the primary molecular mechanism governing the genetic association or could it be an as yet unknown function for this interesting pseudokinase? Is hepatic TRIB1 the sole regulator of lipid metabolism or could extrahepatic TRIB1 play a role as well? The following review summarizes key findings related to these questions and highlights both the challenges and excitement in pursuing translational research of a novel gene in the post-GWAS era.

SUBMITTER: Jadhav KS

PROVIDER: S-EPMC6761832 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trouble With Tribbles-1.

Jadhav Kavita S KS Bauer Robert C RC

Arteriosclerosis, thrombosis, and vascular biology 20190601 6

Genome-wide association studies (GWAS) have identified hundreds of genomic loci in humans that are significantly associated with plasma cholesterol, triglycerides, and coronary artery disease. Although some loci contain genes with known regulatory roles in lipid metabolism and atherosclerosis, the majority were being implicated for the first time. The 8q24 locus, containing the gene TRIB1 ( Tribbles-1), is the only novel GWAS locus that associates with all 4 plasma lipid traits and coronary arte ...[more]

PMID: 31018662

Similar Datasets

Project description:BackgroundRecent studies have attributed adverse local tissue reactions (ALTRs) in patients with total hip arthroplasties (THAs) to tribocorrosion debris generated by modular femoral stems. The presentations of ALTR are diverse, as are the causes of it, and the biological responses can be important reasons for failure after THA.Question/purposes(1) What clinical problems have been reported in patients with modular stems since 1988? (2) What THA design features are associated with tribocorrosion in taper junctions? (3) What are the microscopic and tribological characteristics of the debris produced at the taper junctions? (4) What are the cellular and immunological traits of the biological response to taper tribocorrosion debris?MethodsWe conducted a systematic review using MEDLINE and EMBASE-cited articles to summarize failure modes associated with modular femoral stems. One hundred sixty-two of 1043 articles reported on the clinical performances or failure modes attributed to modular femoral stems. There were 10 laboratory studies, 26 case reports, 13 Level IV, 94 Level III, 18 Level II, and one Level I of Evidence papers. To address the remaining questions, we did a second review of 524 articles. One hundred twenty-seven articles met the eligibility criteria, including 81 articles on design features related to tribocorrosion, 15 articles on corrosion debris characteristics, and 31 articles on the biological response to tribocorrosion debris.ResultsSixty-eight of 162 studies reported failure attributed to modular femoral stems for one of these four modularity-related failure modes: tribocorrosion-associated ALTR, dissociation of a taper junction, stem fracture, and mismatch of a femoral head taper attached to a stem with a different trunnion size. The remaining 94 studies found no clinical consequences related to the presence of a taper junction. THA component features associated with tribocorrosion included trunnion geometry and large-diameter femoral heads. Solid tribocorrosion debris is primarily chromium-orthophosphate material of variable size and may be more biologically reactive than wear debris.ConclusionsThere has been an increase in publications describing ALTR around modular hip prostheses in the last 3 years. Implant design changes, including larger femoral heads and smaller trunnions, have been implicated, but there may also be more recognition of the problem by the orthopaedic community. Analyzing retrieved implants to understand the history of taper-related problems, designing clinically relevant in vitro corrosion tests to test modular junctions, and identifying biomarkers to recognize patients at risk of ALTR should be the focus of ongoing research to help surgeons avoid and detect tribocorrosion-related problems in joint replacements.

Dataset Information

Trouble With Tribbles-1.

Publications

Trouble With Tribbles-1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets