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.
| Original language | English |
|---|---|
| Journal | Human Genetics |
| Volume | 122 |
| Issue number | 1 |
| Pages (from-to) | 95-102 |
| Number of pages | 8 |
| ISSN | 0340-6717 |
| DOIs | |
| Publication status | Published - 01.08.2007 |
Funding
Acknowledgments We thank the members of the families for their participation. Moreover, we thank Ms Daniela Hant; B.S., for expert technical assistance and Alexandru Gurau and Pierre-Luc Brunelle for bioinformatics assistance. U.B. and H.J.J. are supported in part by a grants from NHLBI (1P50 HL65203; 1R01 HL 74321). Moreover, we acknowledge the support by the Wilhelm-Vaillant-Stiftung, the Deutsche Herzstiftung, the National Genome Network (NGFN) of the Bun-desministerium für Bildung und Forschung, the Cullen Family Run (U.B.), and the Deutsche Forschungsgemeinschaft (C.H., S.H., J.E., and H.S.). The statistical genetic analyses reported here were conducted using the program package SOLAR. SOLAR is supported by U.S. Public Health Service grant MH059490 from the National Institutes of Health.
