title: A locus on chromosome 10 influences C-reactive protein levels in two independent populations.
abstract: 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.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. Broeckel@mcw.edu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Bjoern
authors.initials: B
authors.lastname: Mayer
authors.forename: Karen
authors.initials: K
authors.lastname: Maresso
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Ondrej
authors.initials: O
authors.lastname: Seda
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.forename: Stephan
authors.initials: S
authors.lastname: Holmer
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Christian
authors.initials: C
authors.lastname: Glöckner
authors.forename: Michael
authors.initials: M
authors.lastname: Harrison
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Jeff T
authors.initials: JT
authors.lastname: Williams
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Guenter A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: 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
chemical_list: D002097:C-Reactive Protein