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.

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

“…While there have been relatively few linkage studies of CRP [74–76], Ding et al reported a LOD of 0.49 on chr 6, 187cM among African Americans [18], and a LOD score of 1.7 (107cM) on chr 10 [18]. While the present linkage results failed to replicate this chr 10 result in American Indians, a suggestive cluster of SNPs was found approximately 30 Mb proximal to this locus.…”

Polymorphisms of the IL1-Receptor Antagonist Gene ( IL1RN ) Are Associated With Multiple Markers of Systemic Inflammation

“…In a recent genome-wide linkage analysis, the region on chromosome 2 containing IL1RN was identified as influencing CRP levels in European families with early-onset coronary heart disease (CHD). 17 In smaller hospital-based studies of CHD patients, allele 2 of the 86-bp IL1RN VNTR polymorphism was associated with lower plasma CRP and fibrinogen concentration. 18,19 Our findings extend the importance of IL1RN genotype as a determinant of CRP and fibrinogen levels among the general population of younger and older European American adults.…”

“Big Data” in Economic History

“…In common with population registers, big genealogical databases such as BALSAC and the UPDB are particularly suitable for answering historical questions about intergenerational social mobility or transmission of fertility behavior (Gagnon, Tremblay, Vézina, et al 2011; Jennings, Sullivan, and Hacker 2012; Maloney, Hanson, and Smith 2014). These genealogies also provide an essential source of data for the study of inheritance of health and disease (Broeckel, Hengstenberg, Mayer, et al 2007; Kerber, O'Brien, Smith, et al 2001). Martha Bailey's LIFE-M project is now developing geographically broader population linkages of vital records and census data for the late nineteenth and twentieth century United States (Bailey 2017).…”