Familial and genetic determinants of systemic markers of inflammation: The NHLBI family heart study

James S. Pankow, Aaron R. Folsom, Mary Cushman, Ingrid B. Borecki, Paul N. Hopkins, John H. Eckfeldt, Russell P. Tracy

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

Abstract

Inflammation is thought to play a central role in the etiology and outcome of atherosclerosis. Animal studies as well as in vitro and in vivo human studies suggest that host factors modulate the magnitude and extent of inflammatory responses. We investigated familial aggregation of three systemic markers of inflammation (C-reactive protein (CRP), white blood cell count (WBC), and albumin) in a large, cross-sectional study conducted in four US communities. We found evidence of substantial heritability (35-40%) for CRP levels as well as for WBC and albumin levels. Negligible spouse correlations suggested little influence of shared household environment on these traits. The combination of sociodemographic factors (age, center, education), behavioral and lifestyle factors (cigarette smoking, alcohol intake, hormone replacement therapy), obesity and fat patterning, and prevalent diabetes explained 13-30% the interindividual variability of these traits. There was no evidence that these inflammation phenotypes were linked to a microsatellite marker in the interleukin-1 gene cluster on chromosome 2q, a region that includes several candidate genes for chronic inflammatory diseases. Our findings suggest that CRP levels, albumin levels, and WBC are determined at least partially by genetic factors. Further efforts to identify gene loci affecting these traits are warranted.

Original languageEnglish (US)
Pages (from-to)681-689
Number of pages9
JournalAtherosclerosis
Volume154
Issue number3
DOIs
StatePublished - Feb 15 2001

Bibliographical note

Funding Information:
This paper is presented on behalf of the Investigators of the NHLBI Family Heart Study. Participating Institutions and Principal Staff of the study are as follows, Forsyth County/University of North Carolina/Wake Forest University, Gerardo Heiss, Stephen Rich, Greg Evans, James Pankow; H.A. Tyroler, Jeannette T. Bensen, Catherine Paton, Delilah Posey, and Amy Haire; University of Minnesota Field Center, Donna K. Arnett, Aaron R. Folsom, Larry Atwood, James Peacock, Greg Feitl; Boston University/Framingham Field Center, R. Curtis Ellison, Richard H. Myers, Yuqing Zhang, Andrew G. Bostom, Luc Djoussé, Jemma B. Wilk, and Greta Lee Splansky; University of Utah Field Center: Steven C. Hunt, Roger R. Williams (deceased), Paul N. Hopkins, Jan Skuppin and Hilary Coon; Coordinating Center, Washington University, St. Louis, Michael A. Province, D.C. Rao, Ingrid B. Borecki, Yuling Hong, Mary Feitosa, Jeanne Cashman, and Avril Adelman; Central Biochemistry Laboratory, University of Minnesota, John H. Eckfeldt, Greg Rynders, Catherine Leiendecker-Foster, and Michael Y. Tsai; Central Molecular Laboratory, University of Utah, Mark F. Leppert, Jean-Marc Lalouel, Tena Varvil, Lisa Baird; National Heart, Lung, & Blood Institute-Project Office, Phylliss Sholinsky, Millicent Higgins (retired), Jacob Keller (retired), Sarah Knox, and Lorraine Silsbee. This work was supported by National Heart, Lung, and Blood Institute cooperative agreement grants N01-HC-25104, N01-HC-25105, N01-HC-25106, N01-HC-25107, N01-HC-25108, and N01-HC-25109.

Keywords

  • Albumin
  • C-reactive protein
  • Inflammation
  • Interleukin-1
  • White blood cell count

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