Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: the CODAM study

Ying Xin, Elisabeth Hertle, Carla J. H. van der Kallen, Casper G. Schalkwijk, Coen D. A. Stehouwer, Marleen M. J. van Greevenbroek*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Web of Science)

Abstract

PurposeWe investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease.MethodsThe study cohort was comprised of 574 participants (61% men, age 59.67.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n=189) metabolic syndrome.ResultsC3 (odds ratio (OR)=1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR=1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n=40 cases). Notably, in the cross-sectional analyses, we did observe higher levels of C3a (OR=1.25 [1.03; 1.52]), FH (OR=2.93 [2.24; 3.83]), and properdin (OR=1.88 [1.50; 2.34]), in addition to C3 (OR=3.60 [2.73; 4.75]) and C4 (OR=1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH.ConclusionsIn the cross-sectional analyses, the effects sizes (standardized regression coefficients) or C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome.

Original languageEnglish
Pages (from-to)617-627
Number of pages11
JournalEndocrine
Volume62
Issue number3
DOIs
Publication statusPublished - Dec 2018

Keywords

  • Human
  • Complement activation
  • Metabolic syndrome
  • Incidence
  • Longitudinal
  • ACYLATION-STIMULATING PROTEIN
  • ADIPOSE-TISSUE
  • INFLAMMATORY MARKERS
  • INSULIN-RESISTANCE
  • REACTIVE PROTEIN
  • SYSTEM
  • RISK
  • ATHEROSCLEROSIS
  • COMPONENTS
  • EFFECTOR

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