Genetic and environmental influences on the prospective correlation between systemic inflammation and coronary heart disease death in male twins

Sheng Hui Wu, Michael C. Neale, Anthony J. Acton, Robert V. Considine, Ruth E. Krasnow, Terry Reed, Jun Dai

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

OBJECTIVE - Because of lack of evidence, we aimed to examine to what degree low-grade systemic inflammation and coronary heart disease (CHD) death shared common genetic and environmental substrates. APPROACH AND RESULTS - From the 41-year prospective National Heart, Lung, and Blood Institute Twin Study, we included 950 middle-aged male twins at baseline (1969-1973). Low-grade systemic inflammation was measured with plasma levels of interleukin-6 (IL-6) and C-reactive protein. Univariate and bivariate structural equation models were used, adjusted for a risk score for CHD death. The score-adjusted heritability was 19% for IL-6, 27% for C-reactive protein, and 22% for CHD death. The positive phenotypic correlation of IL-6 with CHD death (radjusted=0.27; 95% confidence interval [CI], 0.08-0.43) was driven by additive genetic factors (contribution [relative contribution], 0.30 [111%]) but attenuated by unique environment (-0.03 [-11%]). The genetic correlation between IL-6 and CHD death was 0.74 (95% CI, 0.21-1.00), whereas the unique environmental correlation was -0.05 (95% CI, -0.35 to 0.25). The proportion of genetic variance for CHD death shared with that for IL-6 was 74%. The phenotypic correlation of C-reactive protein with CHD death (radjusted=0.10; 95% CI, -0.02 to 0.22) was explained by additive genetic factors (0.20 [149%]) but was attenuated by the unique environment (-0.09 [-49%]). The genetic correlation of C-reactive protein with CHD death was 0.63 (95% CI, -0.07 to 1.00), whereas the unique environmental correlation was -0.07 (95% CI, -0.29 to 0.17). CONCLUSIONS - Low-grade systemic inflammation, measured by IL-6, and long-term CHD death share moderate genetic substrates that augment both traits.

Original languageEnglish (US)
Pages (from-to)2168-2174
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume34
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • C-reactive protein
  • coronary disease
  • genes
  • interleukin-6
  • mortality
  • twins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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