Heritability and Expression of C‐Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Abstract

SummaryElevated 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.

Heritability of serum hs-CRP concentration and 5-year changes in the Stanislas family study: association with apolipoprotein E alleles

“…The association between the common polymorphisms of APOE gene and the hs-CRP concentration was already reported in the elderly, 18,19 in dyslipidemic adults, 22 in type II diabetes 24 and in families. 12 However, there is no data about association between the APOE genotype and Table A1 in online appendix.…”

“…16,17 Moreover, some other gene polymorphisms were associated with circulating levels of the hs-CRP, the most studied being the common polymorphisms of the apolipoprotein E gene (APOE) (e2, e3, e4) for which an association was confirmed by many authors in adults and elderly. 12,[18][19][20][21][22][23][24] However, no data exist either about APOE genotype-hs-CRP concentration association in children or about effect of these polymorphisms in combination with estimate of heritability component. 12 Thus, in the present analysis, we aimed at reporting on (i) the association between the APOE gene alleles with the serum hs-CRP concentration in adults and also in children, (ii) the familial aggregation of the serum hs-CRP concentration on a sample of French nuclear families and on (iii) the variance-component genetic linkage of this inflammatory factor with the alleles of the APOE gene.…”

Quantification of the Genetic Component of Basal C‐Reactive Protein Expression in SLE Nuclear Families

“…This has indeed been hinted at in existing regression-based analyses where the partial r 2 for associated CRP polymorphisms has been <3% (Crawford et al, 2006;Kathiresan et al, 2006;Lange et al, 2006b). Of potential trans-acting influences, variation at the acute-phase cytokine genes interleukin-1β (IL1B) and interleukin-6 (IL6) and also apolipoprotein E (APOE) has been associated with basal CRP, albeit inconsistently (Berger et al, 2002;Chasman et al, 2006;Eklund et al, 2005;Judson et al, 2004;Lange et al, 2006a;Latkovskis et al, 2004;Marz et al, 2004;Paik et al, 2007;Shin et al, 2007;Vickers et al, 2002).…”

Racial Disparity in Glucagon-Like Peptide 1 and Inflammation Markers Among Severely Obese Adolescents

“…It has been suggested that genetic factors are likely to play a role in the inflammatory response in African Americans (24,25). Genes encoding critical proinflammatory cytokines, such as interleukin-1 and -6 and tumor necrosis factor-␣, have important roles in inflammatory diseases (24).…”