Dataset Information

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

ABSTRACT: OBJECTIVE:Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS:The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS:We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS:This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele.

SUBMITTER: Eiriksdottir G

PROVIDER: S-EPMC3149889 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

Eiriksdottir G G Smith A V AV Aspelund T T Hafsteinsdottir S H SH Olafsdottir E E Launer L J LJ Harris T B TB Gudnason V V

International journal of obesity (2005) 20090113 2

<h4>Objective</h4>Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels.<h4>Methods</h4>The first 2296 ...[more]

PMID: 19139754

Similar Datasets

Project description:OBJECTIVE:To investigate the association between age-related macular degeneration (AMD) and mortality in older persons. DESIGN:Population-based prospective cohort study. PARTICIPANTS:Participants 67 to 96 years of age (43.1% male) enrolled between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study. METHODS:Retinal photographs of the macula were acquired digitally and evaluated for the presence of AMD lesions using the Wisconsin Age-Related Maculopathy grading scheme. Mortality was assessed prospectively through 2013 with cause of death available through 2009. The association between AMD and death, resulting from any cause and specifically cardiovascular disease (CVD), was examined using Cox proportional hazards regression with age as the time scale, adjusted for significant risk factors and comorbid conditions. To address a violation in the proportional hazards assumption, analyses were stratified into 2 groups based on the mean age at death (83 years). MAIN OUTCOME MEASURES:Mortality resulting from all causes and CVD. RESULTS:Among 4910 participants, after a median follow-up of 8.6 years, 1742 died (35.5%), of whom 614 (35.2%) had signs of AMD at baseline. Cardiovascular disease was the cause of death for 357 people who died before the end of 2009, of whom 144 (40%) had AMD (101 with early disease and 43 with late disease). After considering covariates, including comorbid conditions, having early AMD at any age or having late AMD in individuals younger than 83 years (n = 4179) were not associated with all-cause or CVD mortality. In individuals 83 years of age and older (n = 731), late AMD was associated significantly with increased risk of all-cause mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.20-2.57) and CVD-related mortality (HR, 2.37; 95% CI, 1.41-3.98). In addition to having AMD, older individuals who died were more likely to be male and to have low body mass index, impaired cognition, and microalbuminuria. CONCLUSIONS:Competing risk factors and concomitant conditions are important in determining mortality risk resulting from AMD. Individuals with early AMD are not more likely to die than peers of comparable age. Late AMD becomes a predictor of mortality by the mid-octogenarian years.

Project description:PURPOSE:To assess the impact of retinopathy on mortality in older persons with concomitant health conditions. DESIGN:Population-based prospective cohort study. PARTICIPANTS:A total of 4966 individuals aged 67 to 96 years (43.2% were male) from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS). METHODS:Retinopathy was evaluated from digital fundus images (2002-2006) using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Mortality was assessed through September 2013 (cause of death assigned through 2009). Cox proportional hazards regression models, with age as the time scale, estimated the association between retinopathy and death while controlling for risk factors and the presence of concomitant health conditions. MAIN OUTCOME MEASURES:Mortality from all causes and cardiovascular disease (CVD). RESULTS:Among the 4966 participants, 503 (10.1%) had diabetes and 614 (12.4%) had retinopathy at baseline. A subset of these (136 [2.7%]) had both diabetes and retinopathy. After a median follow-up of 8.6 years, 1763 persons died, 276 (45.0%) with retinopathy and 1487 (34.2%) without retinopathy, of whom 76 and 162 persons, respectively, also had diabetes. There were 366 deaths from CVD through 2009, 72 (11.7%) in persons with retinopathy and 294 (6.8%) in those without retinopathy. In multivariable analyses, retinopathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.10-1.43; P < 0.01) and CVD-related mortality (HR, 1.57; 95% CI, 1.20-2.06; P < 0.01). Findings were more striking in men: all-cause HR, 1.33 (95% CI, 1.11-1.60) and CVD HR, 1.81 (95% CI, 1.25-2.63). Risk of mortality was further increased among those with retinopathy concomitant with microalbuminuria (all-cause HR, 1.70; 95% CI, 1.03-2.23, and CVD HR, 2.04; 95% CI, 1.27-3.28) and those with retinopathy, microalbuminuria, and diabetes (all-cause HR, 2.01; 95% CI, 1.22-3.31, and CVD HR, 5.24; 95% CI, 1.91-14.42). History of clinical stroke increased the risk of CVD-related mortality among persons with retinopathy (HR, 3.30; 95% CI, 2.05-5.32), particularly those with retinopathy and diabetes (HR, 5.38; 95% CI, 1.80-16.06). CONCLUSIONS:Even minimal retinopathy was a significant predictor of increased mortality in older persons, particularly men, irrespective of diabetes status. Persons with retinopathy may warrant closer clinical management of general health.

Project description:Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (-0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.

Dataset Information

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

Publications

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets