C-reactive protein, an ‘intermediate phenotype’ for inflammation: human twin studies reveal heritability, association with blood pressure and the metabolic syndrome, and the influence of common polymorphism at catecholaminergic/β-adrenergic pathway loci

Wessel, Jennifer; Moratorio, Guillermo; Rao, Fangwen; Mahata, Manjula; Zhang, Lian; Greene, William L.; Rana, Brinda K.; Kennedy, Brian P.; Khandrika, Srikrishna; Huang, Pauline; Lillie, Elizabeth O.; Shih, Pei-an Betty; Smith, Douglas W.; Wen, Gen; Hamilton, Bruce A.; Ziegler, Michael G.; Witztum, Joseph L.; Schork, Nicholas J.; Schmid‐Schönbein, Geert W.; O’Connor, Daniel T.

doi:10.1097/hjh.0b013e328011753e

Cited by 88 publications

(92 citation statements)

References 71 publications

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“…The most parsimonious model is printed in bold. Jermendy et al, 2011;MacGregor et al, 2004;Rahman et al, 2009;Reed et al, 1994;Sas et al, 2012;Su et al, 2008Su et al, , 2009aSu et al, , 2009bWang et al, 2011;Wessel et al, 2007;Worns et al, 2006) and extend the findings of previous studies by showing that genetic non-additivity is an important factor in explaining individual differences in TNF-␣, CRP, and fibrinogen levels and by ruling out a large role for environmental factors shared by family members.…”

Section: Discussionsupporting

confidence: 86%

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

et al. 2013

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In this study we examined the genetic architecture of variation in the pro-inflammatory state, using an extended twin-family design. Within the Netherlands Twin Register Biobank, fasting Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP), and fibrinogen levels were available for 3,534 twins, 1,568 of their non-twin siblings, and 2,227 parents from 3,095 families. Heritability analyses took into account the effects of current and recent illness, anti-inflammatory medication, female sex hormone status, age, sex, body mass index, smoking status, month of data collection, and batch processing. Moderate broad-sense heritability was found for all inflammatory parameters (39%, 21%, 45%, and 46% for TNF-α, IL-6, CRP and fibrinogen, respectively). For all parameters, the remaining variance was explained by unique environmental influences and not by environment shared by family members. There was no resemblance between spouses for any of the inflammatory parameters, except for fibrinogen. Also, there was no evidence for twin-specific effects. A considerable part of genetic variation was explained by non-additive genetic effects for TNF-α, CRP, and fibrinogen. For IL-6, all genetic variance was additive. This study may have implications for future genome-wide association studies by setting a clear numerical target for genome-wide screens that aim to find genetic variants regulating the levels of these pro-inflammatory markers.

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Section: Discussionsupporting

confidence: 86%

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

et al. 2013

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“…A pesar de estas evidencias a favor de la asociación entre el gen ADRB2 y la hipertensión o presión arterial, otros estudios han fallado al replicar dicha asociación en población caucásica (77,78) y en afroamericanos (79). En el estudio de Aristizábal, et al, en población antioqueña, se evaluó la asociación entre 9 polimorfismos en ADRB2 y la presión arterial elevada, sin encontrarse asociación con ninguno de los SNP (47).…”

Section: Discussionunclassified

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

et al. 2013

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“…7 In view of the importance of hs-CRP concentration, several teams investigated its genetic heritability in various populations of middle-aged adults or elderly. The twin studies estimated genetic heritability ranged between 22 and 56%, [8][9][10][11] while studies based on individuals from large pedigrees showed that polygenic component accounted for lower values (between 28 and 39% of total variance). [12][13][14] However, a recent family study concluded to have no polygenic effect in heritability of hs-CRP level.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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We aimed at estimating additive genetic heritability, household component effect and the influence of common alleles of the apolipoprotein E gene (APOE) on serum high-sensitivity C-reactive protein (hs-CRP) concentrations and the subsequent changes over 5 years. A sub-sample of 320 nuclear families was randomly selected from the Stanislas Family Study. Serum hs-CRP concentration was measured by immunonephelometry at entrance and after 5 years. APOE alleles were determined by restriction fragment length polymorphism. After adjustment for covariates, the number of the e4 allele was negatively associated with serum concentration of hs-CRP in the whole sample, at entrance and 5 years later, without significant interaction with sex by generation groups (P ¼ 0.003 and P ¼ 0.0003, respectively). However, no significant association was found between e4 allele and 5-year changes in hs-CRP concentration. Using a variance component analysis, no significant genetic influence was shown in family aggregation of both hs-CRP measurements and 5-year changes; the household common component was between 6.5 and 12.8%. In addition, after adjustment for APOE gene polymorphisms, degrees of resemblance were almost unchanged. In the Stanislas Family Study, e4 allele of the APOE gene was associated with lower hs-CRP concentration, but not with 5-year changes. However, variance component analysis did not evidence a significant polygenic effect.

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C-reactive protein, an ‘intermediate phenotype’ for inflammation: human twin studies reveal heritability, association with blood pressure and the metabolic syndrome, and the influence of common polymorphism at catecholaminergic/β-adrenergic pathway loci

Cited by 88 publications

References 71 publications

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

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

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