dc.contributor.author | Tornio, A | |
dc.contributor.author | Bigossi, M | |
dc.contributor.author | Siddiqui, MK | |
dc.contributor.author | Kennedy, G | |
dc.contributor.author | Melhem, A | |
dc.contributor.author | Chourasia, MK | |
dc.contributor.author | Maroteau, C | |
dc.contributor.author | Pola, R | |
dc.contributor.author | Chasman, DI | |
dc.contributor.author | Doney, ASF | |
dc.contributor.author | Palmer, CNA | |
dc.date.accessioned | 2024-04-08T07:39:54Z | |
dc.date.available | 2023-02-23 | |
dc.date.available | 2024-04-08T07:39:54Z | |
dc.date.issued | 2023-03-14 | |
dc.identifier.citation | Tornio A, Bigossi M, Siddiqui MK, Kennedy G, Melhem A, Chourasia MK, Maroteau C, Pola R, Chasman DI, Doney ASF and Palmer CNA (2023), The cholesterol-lowering effect of statins is modified by LILRB5 intolerance genotype: Results from a recruit-bygenotype clinical trial. Front. Pharmacol. 14:1090010. doi: 10.3389/fphar.2023.1090010 | en_US |
dc.identifier.other | ARTN 1090010 | |
dc.identifier.other | ARTN 1090010 | |
dc.identifier.other | ARTN 1090010 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/95969 | |
dc.description.abstract | Background/Aims: Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The LILRB5 Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets.
Methods: A double-blind, cross-over, recruit-by-genotype trial was undertaken. A total of 18 participants who had either the Asp247Asp (T/T) genotype or the Gly247Gly (C/C) genotype were recruited to the study. Participants were randomised to receive placebo or atorvastatin 80 mg daily for 28 days. Following a washout period of 3 weeks, they were then switched to the opposite treatment. Biochemical and immunological measurements as well as interviews were performed prior to and after both treatment periods. Within genotype group comparisons were performed using repeated measures Wilcoxon tests. Two-way repeated measures ANOVA with genotype and treatment as factors were used to compare changes in biochemical parameters between groups during placebo and atorvastatin periods.
Results: Individuals with the Asp247Asp genotype had a greater increase in creatine kinase (CK) compared to those with Gly247Gly genotype in response to atorvastatin (p = 0.03). Those with Gly247Gly genotype had a mean non-HDL cholesterol reduction of 2.44 (95% CI:1.59 – 3.29) mmol/L while in Asp247Asp genotype group the mean reduction was 1.28 (95%CI: 0.48 – 2.07) mmol/L. The interaction between the genotype and atorvastatin treatment for total cholesterol (p = 0.007) and non-HDL cholesterol response was significant (p = 0.025). Immunological assessment showed no significant changes in aggregation of T regulatory cells by genotype.
Conclusion: The Asp247Gly variant in LILRB5, previously associated with statin intolerance, was associated with differential increases in creatine kinase and total cholesterol and non-HDL cholesterol-lowering response to atorvastatin. Taken together, these results suggest that this variant could have utility in precision cardiovascular therapy. | en_US |
dc.publisher | Frontiers Media | en_US |
dc.relation.ispartof | FRONTIERS IN PHARMACOLOGY | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.subject | RCT-randomized controlled trial | en_US |
dc.subject | ADR (adverse drug reaction) | en_US |
dc.subject | statin (HMG-CoA reductase inhibitor) | en_US |
dc.subject | treg-regulatory T cell | en_US |
dc.subject | non-HDL cholesterol | en_US |
dc.title | The cholesterol-lowering effect of statins is modified by LILRB5 intolerance genotype: Results from a recruit-by-genotype clinical trial | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2023 Tornio, Bigossi, Siddiqui, Kennedy, Melhem, Chourasia, Maroteau, Pola, Chasman, Doney and Palmer. | |
dc.identifier.doi | 10.3389/fphar.2023.1090010 | |
pubs.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000959424100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 14 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |