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

Berrahmoune, Hind; Herbeth, Bernard; Siest, Gérard; Visvikis‐Siest, Sophie

doi:10.1038/sj.gene.6364395

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…In agreement with other studies we found that serum CRP was lower in subjects with ε4 haplotypes [25,28,29,30]. This association was present after adjusting for other risk factors, such as age, diabetes, CHD and hypertension.…”

Section: Discussionsupporting

confidence: 93%

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

et al. 2010

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Objective Apolipoprotein E (ApoE) genotype has been associated with systemic inflammation and athero-thrombosis however the association with abdominal aortic aneurysm (AAA) has not been previously examined. We assessed the association between ApoE genotype with AAA presence and growth, and serum C-reactive protein (CRP). Methods Serum concentrations of CRP (in 1358 men) and 6 single nucleotide polymorphisms (SNPs) for ApoE (in 1711 men) were examined in subjects from the Health In Men Study. 640 men with small AAAs were followed by ultrasound surveillance for a mean of 4.1 years. Results There was no association between ApoE genotype and AAA presence. Men heterozygote for the ApoE p.Arg176Cys polymorphism had slower AAA growth, odds ratio for AAA progression ≥ median 0.41, 95% confidence intervals 0.21-0.80, p=0.01. Men heterozygote for the ApoE g.50093756A>G polymorphism had slightly more rapid AAA growth, odds ratio for AAA progression ≥ median 1.48, 95% confidence intervals 1.02-2.14, p=0.04. None of the ApoE SNPs were associated with AAA growth however taking into account multiple testing. Two SNPs in ApoE were associated with serum CRP under a co-dominant model, ApoE p.Cys130Arg (SNP ID rs429358), p=0.00003 and ApoE g.50114786A>G (SNP ID rs4420638), p=0.00013. Adjusting for other risk factors plus serum creatinine the ε4 allele was associated with lower serum CRP under a dominant model, coefficient 0.089, p=0.002. Conclusion We found no consistent association between ApoE genotype and AAA. We confirmed an association between ApoE genotype and serum CRP.

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Section: Discussionsupporting

confidence: 93%

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

et al. 2010

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“…7,25,37 In the Stanislas Family Study of 320 nuclear families, variance component analysis did not reveal the presence of a significant genetic effect to variation in hs-CRP. 8 In the Jackson Heart Study, the heritability of hs-CRP in blacks reached 45% after adjustment for age, sex, and BMI. 9 Comparable heritability levels have been reported in Japanese Americans (30%), twins many of which with hypertension (56%) and siblings from the Diabetes Heart Study (37% after adjustment for age, sex, ethnicity, and BMI).…”

Section: Evidence For Genetic Covariation Among Cvd Risk Factorsmentioning

confidence: 99%

Are There Genetic Paths Common to Obesity, Cardiovascular Disease Outcomes, and Cardiovascular Risk Factors?

Rankinen

Sarzynski

Ghosh

et al. 2015

Circulation Research

115

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Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets.

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“…3D). In this instance, a false-negative association may be due to failure to account for a second gene that modifies the levels of the biomarker of interest, e.g., a SNP in the promoter of the IL-6 gene that associates with serum IL-6 levels [31] has been shown to correlate more strongly with CRP than IL-6 levels [32], and ApoE alleles can also influence CRP concentrations [33,34]. Illustrating gene-environmental interactions, a recent study showed that environmental factors modify the effects of the functional IL-6 promoter SNP [35].…”

Section: Considerations For Mendelian Randomizationmentioning

confidence: 99%

Mendelian randomization: potential use of genetics to enable causal inferences regarding HIV-associated biomarkers and outcomes

Castiblanco

Walter³

et al. 2010

Current Opinion in HIV and AIDS

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Purpose of review It is unknown whether biomarkers simply correlate with or are causal for HIV-associated outcomes. Mendelian randomization (MR), is a genetic epidemiologic approach used to disentangle causation from association. Here, we discuss the potential use of MR for differentiating whether biomarkers are correlating with or causal for HIV-associated outcomes. Recent findings MR refers to the random allocation of alleles at the time of gamete formation. In observational epidemiology, this refers to the use of genetic variants to estimate a causal effect between a modifiable risk factor and an outcome of interest. A formal MR study using a genetic marker as a proxy for the biomarker has not been conducted in the HIV field. However, in the post-genomic era this approach is being used increasingly. Examples are evidence for the causal role of body mass index on blood pressure and non-causal role of CRP in coronary heart disease. We discuss the conceptual framework, uses and limitations of MR in the context of HIV infection as well as specific biomarkers (IL-6, CRP) and genetic determinants (e.g., in CCR5, chemokine, and DARC genes) that associate with HIV-related outcomes. Summary Making the distinction between correlation and causality has particular relevance when a biomarker (e.g. IL-6) is potentially modifiable, in which case a biomarker-guided targeted treatment strategy may be feasible. Although the tenets of MR rest on strong assumptions, and conducting an MR study in HIV infection presents many challenges, it may offer the potential to identify causal biomarkers for HIV-associated outcomes.

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

Cited by 12 publications

References 39 publications

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

Are There Genetic Paths Common to Obesity, Cardiovascular Disease Outcomes, and Cardiovascular Risk Factors?

Mendelian randomization: potential use of genetics to enable causal inferences regarding HIV-associated biomarkers and outcomes

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