Dataset Information

Associations of Circulating Protein Levels With Lipid Fractions in the General Population.

ABSTRACT: Objective- Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results- We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels. Conclusions- Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.

SUBMITTER: Figarska SM

PROVIDER: S-EPMC6205762 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations of Circulating Protein Levels With Lipid Fractions in the General Population.

Figarska Sylwia M SM Gustafsson Stefan S Sundström Johan J Ärnlöv Johan J Mälarstig Anders A Elmståhl Sölve S Fall Tove T Lind Lars L Ingelsson Erik E

Arteriosclerosis, thrombosis, and vascular biology 20181001 10

Objective- Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results- We measured plasma protein levels using the Olink ProSeek CVD I ...[more]

PMID: 30354202

Similar Datasets

Project description:Adipocyte fatty acid binding protein (FABP4) has been recently characterized as an adipokine that is closely associated with obesity and metabolic syndrome. Irisin, a novel myokine, activates thermogenesis by increasing the transformation of white adipocytes to brown, and it has improved glucose homeostasis in animal models. In this study, we aimed to explore the relationship between serum FABP4 and irisin in middle-aged Chinese subjects.A total of 111 normal residents (56 men and 55 women) of Fengxian District who were 40 to 60 years of age were recruited. Circulating FABP4 and irisin were determined by enzyme-linked immunosorbent assay. Anthropometric parameters, oral glucose tolerance test results, hemoglobin A1C (HbA1C), blood lipids, homeostasis model assessment of insulin resistance, homeostasis model assessment-β and body fat composition were also determined.All participants were categorized by FABP4 tertiles. There were significant differences in blood pressure, body fat percentage, 2-h plasma glucose, and skeletal muscle mass among the three groups (P<0.05). Furthermore, FABP4 levels in the women were significantly higher than in the men (P<0.05). However, there was no sexual dimorphism in serum irisin (P>0.05). To exclude the effect of sex difference, partial correlations analysis showed that FABP4 was positively correlated with diastolic blood pressure (P<0.05) and body fat percentage (P<0.05) negatively correlated with skeletal muscle mass (P<0.05) and irisin (P<0.05), while irisin was positively correlated with HbA1c (P<0.05) and negatively correlated with creatinine (P<0.05). Multivariate regression analysis demonstrated that serum FABP4 was independently associated with skeletal muscle mass (P<0.001), diastolic blood pressure (P<0.05) and irisin (P<0.05) after adjustment for age, body mass index, body fat percentage, total cholesterol and HbA1C.Elevated FABP4 levels increase the risks of obesity-related metabolic disorders and hypertension. Serum irisin might exert antagonistic effects on FABP4 in the middle-aged Chinese population.

Project description:BACKGROUND:Obese subjects have lower natriuretic peptide levels, but males and females have different anthropometric characteristics and fat distribution. Whether obesity-associated lowering of natriuretic peptides differs among males and females is unknown. Therefore, we investigated sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels among adults in the general population. METHODS AND RESULTS:Using 8260 participants (50.1% females) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, we evaluated the relationship of NT-proBNP levels with obesity-associated parameters, i.e. waist circumference (WC), body mass index (BMI) and body weight in the overall population, and in males and females separately. NT-proBNP levels were higher in females (median, interquartile range: 50.5, 28.2-87.0?ng/L) than in males (24.3, 10.1-54.6?ng/L; P?<?0.001). In the overall population, NT-proBNP levels were significantly lower in heavier individuals and displayed a 'U-shaped' relationship with increasing WC, but were not associated with BMI. After sex stratification, there was no significant association between NT-proBNP concentrations and anthropometric measures in females. However, in males increasing WC and BMI were associated with higher NT-proBNP levels (P?<?0.05) while increasing body weight was associated with slightly lower NT-proBNP levels (P?<?0.05). Age strongly confounded the association of NT-proBNP levels with obesity, and age-associated increases in NT-proBNP were significantly higher in males than in females (P?<?0.001). In multivariable adjusted analyses, the inverse association of obesity and NT-proBNP levels was also significantly modified by sex: NT-proBNP levels were lower with increasing WC, BMI and body weight among females compared with males (Pinteraction ?<?0.05). After also accounting for BMI, abdominal obesity was associated with lower NT-proBNP levels in females, but not in males (Pinteraction ?<?0.001). CONCLUSIONS:Natriuretic peptide deficiency in obesity mostly pertains to females with abdominal obesity, whereas the relationship between obesity and natriuretic peptides appears to be more complex in males.

Project description:BackgroundThe direct effects of general adiposity (body mass index (BMI)) and central adiposity (waist-to-hip-ratio (WHR)) on circulating lipoproteins, lipids, and metabolites are unknown.MethodsWe used new metabolic data from UK Biobank (N=109,532, a five-fold higher N over previous studies). EDTA-plasma was used to quantify 249 traits with nuclear-magnetic-resonance spectroscopy including subclass-specific lipoprotein concentrations and lipid content, plus pre-glycemic and inflammatory metabolites. We used univariable and multivariable two-stage least-squares regression models with genetic risk scores for BMI and WHR as instruments to estimate total (unadjusted) and direct (mutually-adjusted) effects of BMI and WHR on metabolic traits; plus effects on statin use and interaction by sex, statin use, and age (proxy for medication use).FindingsHigher BMI decreased apolipoprotein B and low-density lipoprotein cholesterol (LDL-C) before and after WHR-adjustment, whilst BMI increased triglycerides only before WHR-adjustment. These effects of WHR were larger and BMI-independent. Direct effects differed markedly by sex, e.g., triglycerides increased only with BMI among men, and only with WHR among women. Adiposity measures increased statin use and showed metabolic effects which differed by statin use and age. Among the youngest (38-53y, statins-5%), BMI and WHR (per-SD) increased LDL-C (total effects: 0.04-SD, 95%CI=-0.01,0.08 and 0.10-SD, 95%CI=0.02,0.17 respectively), but only WHR directly. Among the oldest (63-73y, statins-29%), BMI and WHR directly lowered LDL-C (-0.19-SD, 95%CI=-0.27,-0.11 and -0.05-SD, 95%CI=-0.16,0.06 respectively).InterpretationExcess adiposity likely raises atherogenic lipid and metabolite levels exclusively via adiposity stored centrally, particularly among women. Apparent effects of adiposity on lowering LDL-C are likely explained by an effect of adiposity on statin use.FundingUK Medical Research Council; British Heart Foundation; Novo Nordisk; National Institute for Health Research; Wellcome Trust; Cancer Research UK.

Dataset Information

Associations of Circulating Protein Levels With Lipid Fractions in the General Population.

Publications

Associations of Circulating Protein Levels With Lipid Fractions in the General Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets