Statin Therapy Is Associated with Reduced Clonal Expansion in TET2 Mutated Clonal Haematopoiesis of Indeterminate Potential

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.1283-1283
• Main Authors: Nuttall Musson, Ellen, Hoade, Yvette, Dace, Phoebe, Brown, Helen, Hill, Madison, Lubin, Alexandra, Miller, Katie-Jo, Zhu, Catherine, Herrero, Javier, Steptoe, Andrew, Denaxas, Spiros, Payne, Elspeth
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-203136

Introduction: Clonal haematopoiesis of indeterminate potential (CHIP) is the acquisition of somatic mutations in leukaemia associated genes in haematopoietic progenitors with age. It increases the risk of haematological malignancy, cardiovascular disease and mortality. CHIP-associated inflammation is thought to drive CHIP clonal expansion, with larger clones posing higher risks of adverse health outcomes. Many commonly prescribed medications have anti-inflammatory properties, but their effect on CHIP clone size has not been reported. This analysis characterises the English Longitudinal Study of Ageing (ELSA), a longitudinal cohort of individuals aged >50 running since 2002, as a novel CHIP cohort and investigates the effect of biomedical parameters, comorbidities and prescribed medication on TET2 CHIP clone size. Methods: DNA was extracted from 13270 ELSA peripheral blood samples and sequenced with a custom myeloid amplicon panel. Individuals with samples collected between 2017-2019 were used in these analyses. To validate epidemiological associations in the ELSA cohort, CHIP cases and controls were matched for age, sex and smoking status and odds ratios (OR) of common comorbidities were calculated. To identify determinants of TET2 CHIP clone size, individuals with TET2 CHIP were split 70:30% into test and train cohorts. Stepwise forward regression was used to identify the most important predictors of high variant allele frequency (VAF) (>=10%) versus low VAF (