ORCID Profile
0000-0001-7888-7180
Current Organisation
University of Oxford
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Publisher: American Society for Clinical Investigation
Date: 17-05-2021
DOI: 10.1172/JCI127884
Publisher: Public Library of Science (PLoS)
Date: 04-03-2021
DOI: 10.1371/JOURNAL.PONE.0248043
Abstract: Abdominal aortic aneurysms (AAA) are associated with systemic inflammation and endothelial dysfunction. We previously reported flow mediated dilatation (FMD) of the brachial artery as a predictor of AAA growth. We hence hypothesised that other physical characteristics of the brachial artery correlate with AAA growth. Using a prospectively cohort of AAA patients, we devised a ‘brachial artery relaxation index’ (BARI) and examined its role as a biomarker for AAA growth. However, no correlation between BARI and future aneurysm growth was observed (p = 0.45). Therefore, our investigations did not substantiate the hypothesis that other physical characteristics of the brachial artery predicts AAA growth.
Publisher: Cold Spring Harbor Laboratory
Date: 02-11-2020
DOI: 10.1101/2020.10.31.363291
Abstract: Abdominal aortic aneurysms (AAA) are associated with systemic inflammation and endothelial dysfunction. We previously reported flow mediated dilatation (FMD) of the brachial artery as a predictor of AAA growth. We hence hypothesised that other physical characteristics of the brachial artery correlate with AAA growth. Using a prospectively cohort of AAA patients, we devised a ‘brachial artery relaxation index’ (BARI) and examined its role as a biomarker for AAA growth. However, no correlation between BARI and future aneurysm growth was observed (p=0.5). Therefore, our investigations did not substantiate the hypothesis that other physical characteristics of the brachial artery predicts AAA growth.
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2020
DOI: 10.1101/2020.05.14.095653
Abstract: Varicose veins (VVs) affect one-third of Western society, with a significant subset of patients developing venous ulceration, and ongoing management of venous leg ulcers costing around $14.9 billion annually in the USA. There is no current medical management for VVs, with approaches limited to compression stockings, ablation techniques, or open surgery for more advanced disease. A significant proportion of patients report a positive family history, and heritability is ~17%, suggesting a strong genetic component. We aimed to identify novel therapeutic targets by improving our understanding of the aetiopathology and genetic architecture of VVs. We performed the largest two-stage genome-wide association study of VVs in 401,656 subjects from UK Biobank, and replication in 408,969 subjects from 23andMe (total 135,514 varicose veins cases and 675,111 controls). We constructed a genetic risk score for VVs to investigate its use as a prognostic tool. Genes and pathways were prioritised using a suite of bioinformatic tools, and therapeutic targets identified using the Open Targets Platform. We discovered 49 signals at 46 susceptibility loci associated with VVs, including 29 previously unreported genetic associations (28 susceptibility loci). We demonstrated that patients with VVs requiring surgery have a higher genetic risk score than those managed non-surgically. We map 237 genes to these loci, many of which are biologically relevant and tractable to therapeutic targeting or repurposing (notably VEGFA , COL27A1 , EFEMP1 , PPP3R1 and NFATC2 ). Tissue enrichment analyses implicated vascular tissue, and several genes were enriched in biological pathways relating to extracellular matrix biology, inflammation, angiogenesis, lymphangiogenesis, vascular smooth muscle cell migration, and apoptosis. Genes and pathways identified represent biologically plausible contributors to the pathobiology of VVs, identifying promising candidates for further investigation of venous biology and potential therapeutic targets. We have provided the proof-of-principle that genetic risk score correlates with disease severity, which represents a first step in personalised medicine approaches to varicose veins.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ashok Handa.