≪b>clonal Hematopoiesis of Indeterminate Potential (CHIP) and Incident Type 2 Diabetes (T2D) Risk</b>

openalex(2023)

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摘要
Objective: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident T2D is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.Research Design and Methods: CHIP was derived from whole genome sequencing of blood DNA in NHLBI Trans-omics for Precision Medicine (TOPMed) prospective cohorts. We analyzed 17,637 participants from 6 cohorts, without prior T2D, cardiovascular disease, or cancer. We evaluated baseline CHIP vs. no CHIP prevalence with incident T2D, including associations with DNMT3A, TET2, ASXL1, JAK2, and TP53 variants. We estimated multivariable-adjusted hazard ratios and 95% confidence intervals (HR [CI]) adjusted for age, sex, body mass index, smoking, alcohol, education, self-reported race/ethnicity, and combined cohorts’ estimates via fixed effects meta-analysis.Results: Mean age was 63.4 years (SD=11.5), 76% were female, and CHIP prevalence was 6.0% (n=1,055) at baseline. T2D was diagnosed in n=2,467 over mean follow-up of 9.8 years. Participants with CHIP had a 23% (1.04, 1.45) higher risk of T2D than those with no CHIP. Specifically, TET2 (HR=1.48; 1.05, 2.08) and ASXL1 (HR=1.76; 1.03, 2.99) mutations were at higher T2D risk, and DNMT3A was non-significant (HR=1.15; 0.93, 1.43); statistical power was limited for JAK2 and TP53 analyses.Conclusions: CHIP was associated with higher incidence of T2D. CHIP mutations located on genes implicated in CHD and mortality were also related to T2D, suggesting shared aging-related pathology.
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Clonal Hematopoiesis
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