Submitted on March 1, 2005
Accepted on June 5, 2006
A Quantitative Trait Locus on Chromosome 20q13 for Plasma Levels of C-Reactive Protein in Healthy Whites: The HERITAGE Family Study
Timo A. Lakka1*, Tuomo Rankinen2, Treva Rice3, Arthur S. Leon4, D.C. Rao5, James S. Skinner6, and Claude Bouchard7
1 Department of Physiology, University of Kuopio, Institute of Biomedicine, Kuopio, Finland
2 Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, United States
3 Division of Biostatistics, Washington University School of Medicine, St. Louis, United States
4 School of Kinesiology, University of Minnesota, Minneapolis, Minnesota, United States
5 Division of Biostatistics, Washington University School of Medicine, St. Louis, United States; Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, United States
6 Department of Kinesiology, Indiana University, Bloomington, United States
7 Executive Director, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
* To whom correspondence should be addressed. E-mail: timo.lakka{at}uku.fi.
C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30-40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unknown. We performed a genome-wide linkage scan for plasma CRP levels in healthy Whites from the HERITAGE Family Study. CRP was measured with a high-sensitivity assay. Multipoint linkage analyses were performed in 280 sibling pairs with 654 markers using regression and variance components-based methods. Data were adjusted for independent correlates of plasma CRP. of We showed the strongest evidence of linkage for plasma CRP levels on chromosome 20q13. Markers which gave suggestive linkages in this region were D20S52 (LOD score 3.18, P=0.00006), D20S857 (LOD score 2.87, P=0.00014), D20S869 (LOD score 2.75, P=0.0002), D20S480 (LOD score 2.59, P=0.0003), D20S501 (LOD score 2.55, P=0.0003), D20S840 (LOD score 2.18, P=0.0008), and D20S876 (LOD score 2.07, P=0.001). We also detected suggestive linkage on chromosome 5p13 for marker D5S1470 (LOD score 2.23, P=0.0007). Chromosome 20q13 may contribute to plasma CRP levels in healthy Whites. This region contains genes that are important in the inflammatory process and may play a role in the development of chronic inflammatory diseases. The present findings may be useful in the ongoing effort to search for genes contributing to inflammation and to identify individuals at an increased risk of chronic inflammatory diseases.
