Relationships of complement components C3 and C4 and their genetics to cardiometabolic risk in healthy, non-Hispanic white adolescents.
Adiposity
Adolescent
Age Factors
Body Mass Index
Cardiometabolic Risk Factors
Child
Complement C3
/ genetics
Complement C4
/ genetics
Complement C4a
/ genetics
Complement C4b
/ genetics
Cross-Sectional Studies
DNA Copy Number Variations
Female
Gene Dosage
Humans
Male
Polymorphism, Single Nucleotide
Prospective Studies
Risk Assessment
Vascular Stiffness
Waist Circumference
White People
/ genetics
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
29
03
2019
accepted:
25
07
2019
revised:
18
07
2019
pubmed:
14
8
2019
medline:
26
1
2021
entrez:
13
8
2019
Statut:
ppublish
Résumé
Complement promotes inflammatory and immune responses and may affect cardiometabolic risk. This study was designed to investigate the effect of complement components C3 and C4 on cardiometabolic risk in healthy non-Hispanic white adolescents. Body mass index (BMI), BMI percentile, waist circumference, and percent body fat were assessed in 75 adolescents. Arterial stiffness was assessed using arterial tomography and endothelial function using reactive hyperemia. Fasting lipids, inflammatory markers, and complement levels were measured and oral glucose tolerance test was performed. A single C3 polymorphism and C4 gene copy number variations were assessed. C3 plasma levels increased with measures of obesity. Endothelial function worsened with increased C3 and C4 levels. Triglycerides and low-density lipoprotein increased and high-density lipoprotein (HDL) and insulin sensitivity decreased with increasing C3 levels, but the relationships were lost when body habitus was included in the model. C4 negatively related to HDL and positively to inflammatory markers. Subjects with at least one C3F allele had increased BMI and fat mass index. HDL was significantly related to C4L, C4S, C4A, and C4B gene copy number variation. C3 levels increase with increasing body mass and increased C4 levels and copy number are associated with increased cardiometabolic risk in healthy adolescents.
Sections du résumé
BACKGROUND
Complement promotes inflammatory and immune responses and may affect cardiometabolic risk. This study was designed to investigate the effect of complement components C3 and C4 on cardiometabolic risk in healthy non-Hispanic white adolescents.
METHODS
Body mass index (BMI), BMI percentile, waist circumference, and percent body fat were assessed in 75 adolescents. Arterial stiffness was assessed using arterial tomography and endothelial function using reactive hyperemia. Fasting lipids, inflammatory markers, and complement levels were measured and oral glucose tolerance test was performed. A single C3 polymorphism and C4 gene copy number variations were assessed.
RESULTS
C3 plasma levels increased with measures of obesity. Endothelial function worsened with increased C3 and C4 levels. Triglycerides and low-density lipoprotein increased and high-density lipoprotein (HDL) and insulin sensitivity decreased with increasing C3 levels, but the relationships were lost when body habitus was included in the model. C4 negatively related to HDL and positively to inflammatory markers. Subjects with at least one C3F allele had increased BMI and fat mass index. HDL was significantly related to C4L, C4S, C4A, and C4B gene copy number variation.
CONCLUSIONS
C3 levels increase with increasing body mass and increased C4 levels and copy number are associated with increased cardiometabolic risk in healthy adolescents.
Identifiants
pubmed: 31404919
doi: 10.1038/s41390-019-0534-1
pii: 10.1038/s41390-019-0534-1
pmc: PMC6962538
mid: NIHMS1536753
doi:
Substances chimiques
C3 protein, human
0
Complement C3
0
Complement C4
0
Complement C4a
80295-49-4
Complement C4b
80295-50-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-94Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR073311
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001070
Pays : United States
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