Genetic and environmental influences on systemic markers of inflammation in middle-aged male twins

Atherosclerosis. 2008 Sep;200(1):213-20. doi: 10.1016/j.atherosclerosis.2007.12.009. Epub 2008 Feb 20.

Abstract

Objectives: The aims of this study were to determine the relative influence of genetic and environmental contributions to inflammatory biomarkers, and to what extent correlations among these markers are due to genetic or environmental factors.

Methods: We performed univariate and multivariate genetic analyses of four inflammatory markers: interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), C-reactive protein (CRP), and fibrinogen, in 166 (88 monozygotic and 78 dizygotic) middle-aged male twin pairs.

Results: The mean age (+/-S.D.) of the twins was 54 (+/-2.93) years. Heritability was substantial for CRP (0.61, 95% CI: 0.47-0.72) and moderate to fair for IL-6 (0.31, 0.13-0.46), sIL-6R (0.49, 0.30-0.76) and fibrinogen (0.52, 0.34-0.65). IL-6, CRP and fibrinogen showed significant correlations, but not with sIL-6R. Multivariate genetic analysis found that these correlations could be best explained by a common pathway model, where the common factor explained 27%, 73% and 25% of the variance of IL-6, CRP and fibrinogen, respectively. About 46% (95% CI: 21-64%) of the correlations among the three inflammatory markers could be explained by the genetic factors. After adjusting for covariates known to influence inflammation levels, heritability estimates were slightly decreased but the overall results remained similar.

Conclusions: A significant part of the variation in inflammatory marker levels is due to genetic influences. Furthermore, almost 50% of the shared variance among these biomarkers is due to a common genetic factor which likely plays a key role in the regulation of inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / genetics
  • Fibrinogen / genetics
  • Humans
  • Inflammation / genetics*
  • Interleukin-6 / genetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Receptors, Interleukin-6 / genetics
  • Twins

Substances

  • Biomarkers
  • Interleukin-6
  • Receptors, Interleukin-6
  • Fibrinogen
  • C-Reactive Protein