Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT)

Abstract

BackgroundSerine plays a key role in numerous cellular processes, the levels and metabolism is therefore of critical importance. However, few data are available to illustrate the association of serine with long-term health effects, especially, the predictive value for long-term mortality.ObjectiveThis study was conducted to evaluate the relationship between serum serine levels and all-cause mortality in general hypertensive patients in a longitudinal cohort, and to examine the potential effect modifiers.MethodsA nested case-control (NCC) study was conducted utilizing 20702 hypertensive participants from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, actively controlled trial conducted from May 2008 to August 2013 in China. The current study included 291 cases of all-cause mortality and 291 controls matched on age (≤ 1 year), sex and treatment group. All-cause mortality was the main outcome in this analysis, which included death due to any reason.ResultsWith the increase in serum serine levels, the risk of all-cause mortality first increased before flattening. After adjusting for related variables, the risk of mortality increased significantly with the increase of serum serine levels. Compared with group Q1, the mortality risk of group Q2, Q3 and Q4 were significantly increased [ORs, 95% CI: Q2: 2.32, (1.32–4.07); Q3: 2.59, (1.48–4.54); and Q4: 1.85, (1.07–3.22)]. In the exploratory analysis, we observed three effect modifiers, total homocysteine, 5-Methyltetrahydrofolate, and estimated glomerular filtration rate significantly modified the serum serine and all-cause mortality association.ConclusionSerum serine levels were significantly associated with an increased risk of all-cause mortality in hypertensive patients. Our results and findings, if confirmed further, suggest that serum serine should be considered as a marker for screening risk factors of mortality.Clinical Trial Registration[https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.], identifier [CSPPT, NCT00794885].

Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals

“…We observed beneficial associations between two amino acids ( l -serine and l -glutamine) and cardiovascular mortality and a harmful association for amino acid 4-acetamidobutanoic acid. The inverse association for l -serine in our analyses did not corroborate the previous study where higher serum serine was associated with an increased risk of all-cause mortality among hypertensive patients 23 . However, experimental studies reported an antihypertensive effect of l -serine, suggesting its favorable cardiovascular effects 24 .…”

Bacterial vampirism mediated through taxis to serum

“…We next used CIRA to examine responses to purified effectors diluted in buffer. The concentration of L-serine in human serum ranges from approximately 100-400 µm, depending on diet and health factors [37][38][39] , whereas the neurotransmitter NE, and its metabolized form, DHMA, are thought to circulate at approximately 10 nM 40,41 . It has been proposed that, like L-serine, NE and/or DHMA are sensed directly by Tsr and at even higher (nanomolar) affinity 42,43 .…”

“…To identify the specific chemoattractants driving Tsr-mediated serum chemoattraction, we used CIRA to examine responses to purified effectors diluted in buffer. The concentration of L-serine in human serum ranges from approximately 100-400 µm, depending on diet and health factors (He et al, 2022;Miller et al, 2020;Pitkänen et al, 2003), whereas the neurotransmitters NE, and its metabolized form, DHMA, are thought to circulate at 10,000-fold lower concentrations, approximately 10 nM (Kopin et al, 1978;Steuer et al, 2016). Nevertheless, it has been proposed that NE and/or DHMA are sensed directly by Tsr with nanomolar affinity (Orr et al, 2020;Pasupuleti et al, 2014).…”