KDM5B

THURSDAY, June 27, 2024 -- Rare predicted loss-of-function (pLOF) variants and a polygenic risk score (PRS) are associated with increased atrial fibrillation (AF) risk, according to a study published online June 26 in JAMA Cardiology . Oliver B. Vad, M.D., from Copenhagen University Hospital–Rigshospitalet in Denmark, and colleagues examined rare pLOF variants associated with AF and elucidated their role in risk of AF, cardiomyopathy, and heart failure in combination with a PRS in a genetic association and nested case-control study. Data were included for 403,990 individuals from the U.K. Biobank (median age, 58 years). Over a median follow-up of 13.3 years, 24,447 participants were diagnosed with incident AF. The researchers identified associations for rare pLOF variants in six genes ( TTN , RPL3L , PKP2 , CTNNA3 , KDM5B , and C10orf71 ) with AF. In an external cohort, TTN , RPL3L , PKP2 , CTNNA3 , and KDM5B were replicated. Rare pLOF variants combined with high PRS conferred an odds ratio of 7.08 for AF. PRS carriers also had a considerable 10-year risk of AF (16 and 24 percent in women and men older than 60 years, respectively). There was an association seen for rare pLOF variants with increased risk of cardiomyopathy before and subsequent to AF (hazard ratios, 3.13 and 2.98, respectively). "These findings may contribute to possible future genetic risk stratification and improved clinical practice," the authors write. Several authors disclosed ties to the biopharmaceutical and medical device industries. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

A gene previously linked to intellectual disability has been found to regulate learning and memory in mice. A gene previously linked to intellectual disability has been found to regulate learning and memory in mice. The gene, called KDM5B has previously been linked to some intellectual disability disorders and autism. In the general population, some variants are also associated with reduced brain function, although not sufficient to cause an overt disability or behavioural symptoms. Now, researchers at King's College London, the University of Exeter and the University of California Irvine have found that reduced function of the gene in the brain results in loss of learning ability and memory and a reduction in the brain's ability to strengthen connections between neurons, which is key in the formation of memories. The team's new mouse study, published in the Journal of Neuroscience describes how mice bred without a fully functional KDM5B gene have worse learning and memory abilities. In order to rule out the possibility that the effect may have been caused by an impact on brain development, the researchers also reduced the amount of this gene in a separate group of adult mice, in the hippocampus, a brain region responsible for memory. They found that reduced gene function resulted in epileptic seizures in some mice and a deterioration of their learning and memory. Laboratory experiments suggested that the strengthening of connections between neurons during memory formation was reduced. Professor Albert Basson, whose research group began the work at King's College London and has since moved to the University of Exeter, said: "Memory and the ability to learn are fundamental to our intellectual potential, yet we still have a lot to learn about the underpinning mechanisms. For more than a decade, the KDM5B gene has been linked to autism and some forms of intellectual disability, but a mutation in this gene alone is not always sufficient to cause these conditions, so it hasn't been studied in detail. Our work shows that KDM5B is important for learning and memory and provides new insight into the fundamental mechanisms of memory and learning, which is crucial on the pathway to finding new ways to improve these functions." KDM5B can modify the structure of the genetic material in our cells which determines whether genes necessary for brain development or function are expressed at the correct amount at the right time. Dr Leticia Peres-Sisquez who performed the research at King's College London, said: "We set out to investigate whether KDM5B's ability to modify genetic material has a direct impact on learning and memory. We've discovered that the gene has a direct impact on learning and memory -- which is distinct from any effect during brain development. This gene will now be of much greater interest to researchers on the quest for new treatments for conditions including autism, and other intellectual disability disorders." The research was funded by the Medical Research Council and the National Institutes of Aging, with support from Wellcome. The study is entitled 'The intellectual disability risk gene Kdm5b regulates long term memory consolidation in the hippocampus', published in the Journal of Neuroscience.