Abstract

Introduction: C-reactive protein (CRP) and GlycA are established biomarkers of inflammation. Regular exercise tends to decrease CRP and GlycA levels. However, the molecules underlying CRP and GlycA and their responses to exercise training are less known. Hypothesis: We hypothesized that distinct protein signatures exist for both baseline levels and exercise responsiveness of CRP and GlycA, however with some overlap of proteins across signatures. Methods: Measures were performed before and after 20 weeks of exercise training in 652 Black and White adults from the HERITAGE Family Study. 4,979 circulating proteins were measured using SomaScan. High-sensitivity CRP was measured using automated assays. GlycA was quantified by NMR spectroscopy (LabCorp). Linear mixed models were used to test: 1) Association of baseline proteins with baseline hsCRP and GlycA and 2) Association of change in protein with changes in hsCRP and GlycA. Models were adjusted for age, sex, race, BMI, with family membership as a random variable, with change models also adjusting for baseline trait value. Significance was determined as FDR<0.05. Results: Baseline levels (r=0.51, p<0.0001) and change (r=0.31, p<0.0001) of hsCRP and GlycA were moderately correlated. hsCRP did not change with training, while GlycA trended towards decreasing (Table 1). Across time points, 388 and 1746 unique proteins were associated with hsCRP and GlycA, respectively, with substantial overlap across traits and time points (Table 1). The CRP protein was the top association in 3 of 4 models (range: 1.4x10 -40 < p < 1.2x10 -08 ), with serum amyloid A-2 and A-1 (SAA2, SAA) among the top 6 hits for 3 of 4 models (Table 1). Conclusions: More unique proteins were associated with GlycA levels at both timepoints, with most hsCRP proteins overlapping with GlycA proteins. Overall, a substantial number of proteins are associated with CRP and GlycA levels regardless of when they are measured, which has potential implications for using proteins as signatures of these inflammatory biomarkers.

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