Genetic analysis of hsCRP in American Indians: The Strong Heart Family Study

Autoři: Lyle G. Best aff001;  Poojitha Balakrishnan aff002;  Shelley A. Cole aff003;  Karin Haack aff003;  Jonathan M. Kocarnik aff004;  Nathan Pankratz aff005;  Matthew Z. Anderson aff006;  Nora Franceschini aff008;  Barbara V. Howard aff009;  Elisa T. Lee aff011;  Kari E. North aff012;  Jason G. Umans aff009;  Joseph M. Yracheta aff001;  Ana Navas-Acien aff013;  V. Saroja Voruganti aff014
Působiště autorů: Missouri Breaks Industries Research Inc. Eagle Butte, SD, United States of America aff001;  School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America aff002;  Texas Biomedical Research Institute, San Antonio, TX, United States of America aff003;  Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America aff004;  Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States of America aff005;  Department of Microbiology, Ohio State University, Columbus, OH, United States of America aff006;  Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States of America aff007;  Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States of America aff008;  MedStar Health Research Institute, Hyattsville, MD, United States of America aff009;  Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, United States of America aff010;  College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America aff011;  University of North Carolina, Gillings School of Global Public Health, Chapel Hill, NC, United States of America aff012;  Department of Environmental Health Sciences, Columbia University, New York, NY, United States of America aff013;  Department of Nutrition and Nutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America aff014
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive association between SNPs increasing CRP expression and risk of colon cancer (but thus far not CVD). The effects of individual genetic variants often interact with the genetic background of a population and hence we sought to resolve the genetic determinants of serum CRP in a number of American Indian populations.


The Strong Heart Family Study (SHFS) has serum CRP measurements from 2428 tribal members, recruited as large families from three regions of the United States. Microsatellite markers and MetaboChip defined SNP genotypes were incorporated into variance components, decomposition-based linkage and association analyses.


CRP levels exhibited significant heritability (h2 = 0.33 ± 0.05, p<1.3 X 10−20). A locus on chromosome (chr) 6, near marker D6S281 (approximately at 169.6 Mb, GRCh38/hg38) showed suggestive linkage (LOD = 1.9) to CRP levels. No individual SNPs were found associated with CRP levels after Bonferroni adjustment for multiple testing (threshold <7.77 x 10−7), however, we found nominal associations, many of which replicate previous findings at the CRP, HNF1A and 7 other loci. In addition, we report association of 46 SNPs located at 7 novel loci on chromosomes 2, 5, 6(2 loci), 9, 10 and 17, with an average of 15.3 Kb between SNPs and all with p-values less than 7.2 X 10−4.


In agreement with evidence from other populations, these data show CRP serum levels are under considerable genetic influence; and include loci, such as near CRP and other genes, that replicate results from other ethnic groups. These findings also suggest possible novel loci on chr 6 and other chromosomes that warrant further investigation.

Klíčová slova:

Cardiovascular diseases – Genetic loci – Genome-wide association studies – Heredity – Linkage analysis – Linkage disequilibrium – Molecular genetics


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