A locus on chromosome 10 influences C-reactive protein levels in two independent populations.
High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.
Broeckel
Ulrich
U
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. Broeckel@mcw.edu
Hengstenberg
Christian
C
Mayer
Bjoern
B
Maresso
Karen
K
Gaudet
Daniel
D
Seda
Ondrej
O
Tremblay
Johanne
J
Holmer
Stephan
S
Erdmann
Jeanette
J
Glöckner
Christian
C
Harrison
Michael
M
Martin
Lisa J
LJ
Williams
Jeff T
JT
Schmitz
Gerd
G
Riegger
Guenter A J
GA
Jacob
Howard J
HJ
Hamet
Pavel
P
Schunkert
Heribert
H
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002170:Canada; D002879:Chromosomes, Human, Pair 10; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D005060:Europe; D005190:Family; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D040641:Quantitative Trait Loci
D002097:C-Reactive Protein