Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study.
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.
Pankow
J S
JS
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, 137 East Franklin St., Suite 306, Chapel Hill, NC 27514, USA. jim_pankow@unc.edu
Folsom
A R
AR
Cushman
M
M
Borecki
I B
IB
Hopkins
P N
PN
Eckfeldt
J H
JH
Tracy
R P
RP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003430:Cross-Sectional Studies; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007958:Leukocyte Count; D018895:Microsatellite Repeats; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis*
D015415:Biomarkers; D012709:Serum Albumin; D002097:C-Reactive Protein