title: Heritability and expression of C-reactive protein in type 2 diabetes in the Diabetes Heart Study.
abstract: Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 +/- 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Kathryn
authors.initials: K
authors.lastname: Burdon
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Beck
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: K Bridget
authors.initials: KB
authors.lastname: Brosnihan
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D001741:Black or African American; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
chemical_list: D001057:Apolipoproteins E; D002097:C-Reactive Protein