Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein.

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes

Uric acid and inflammatory markers.

Aims—The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. Methods and results—We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of personsaged 65–95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) were measured. Complete information on potential confounders was collected using standard methods. WBC (P = 0.0001), neutrophils (P < 0.0001), C-reactive protein (P < 0.0001), IL-1ra (P < 0.0001), IL-6 (P = 0.0004), sIL-6r (P = 0.002), IL-18 (P < 0.0001), TNF-α (P = 0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P = 0.004) and IL-6 (P = <0. 0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C- reactive protein, IL-6, IL-1ra, IL-18, and TNF-α, whereas non-significant trends were observed for WBC (P = 0.1) and sIL-6r (P = 0.2). Conclusion—A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintile

Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study.

Background: Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders. Methods: Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowestquartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 μg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results: Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88- 2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12- 4.68), respectively (test for trend, P_.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P_.001). Conclusions: Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons

Desempenho animal em pasto de aveia e azevém com distintas biomassas de lâminas foliares Animal performance in oat and Italian ryegrass pastures under leaf lamina biomass levels

O objetivo deste trabalho foi avaliar o efeito de biomassas de lâminas foliares no desempenho animal. Utilizou-se mistura de aveia (Avena strigosa Schreb) e azevém (Lolium multiflorum Lam.), para determinar quantidades adequadas de sua biomassa no manejo da pastagem. Foram realizados dois experimentos, na estação fria de 2002 e 2003. Na avaliação de 2002, os valores de biomassa de lâminas foliares foram de 360 kg ha-1 (baixa) e 630 kg ha-1 (alta). Em 2003, foram obtidas biomassas de 352, 422 e 507 kg ha-1, classificadas como baixa, média e alta, respectivamente. O método de pastejo foi contínuo, com taxa de lotação variada; os animais utilizados foram terneiros da raça Charolês e cruzados com Nelore, com idade inicial de nove meses. As variáveis de produção animal avaliadas, nos dois anos, foram: ganho médio diário, carga animal e ganho de peso vivo por área. As distintas biomassas de lâminas foliares mantidas não são fatores limitantes ao desempenho animal.<br>The objective of this work was to evaluate the effect of different leaf lamina biomass over animal performance. A mixture of oat (Avena strigosa Schreb) and Italian ryegrass (Lolium multiflorum Lam.) was used to determine adequate levels of leaf lamina biomass for pasture management. Two trials were made, in 2002 and 2003 cool seasons. In 2002 evaluation, leaf lamina biomass values were of 360 kg ha-1 (low) and 630 kg ha-1 (high). In 2003, values obtained for leaf lamina biomasses were of 352, 422 and 507 kg ha-1, being classified as low, medium and high, respectively. Grazing method was continuous, with variable stocking rate; testing animals were calves of Charolais breed and its crosses with Nelore breed, with initial age of nine months. Evaluated variables in animal production, in both years, were: average daily gain, stocking rate and live weight gain per area. Leaf lamina biomasses evaluated are not limiting factors to animal performance

Structural and morphogenical characteristics of black oats and Italian ryegrass on pasture submitted to two grazing intensities Características estruturais e morfogênicas de aveia-preta e azevém-anual em pastagem submetida a duas intensidades de pastejo

Morphogenical and structural characteristics of black oats (Avena strigosa Schreb.) and Italian ryegrass (Lolium multiflorum Lam.) on pastures managed under two grazing intensities were quantified by using marked tiller technique. The expected intensities of disappearance of forage mass initial value were 35% (low) and 65% (high). Experimental animals were sheep and interval among grazing was determined through 300 degree-day thermal sum. The experimental design was completely randomized with two grazing intensities and two replicates. Leaf blades of oats and ryegrass were removed at an average proportion of 57.5% of their initial length for both grazing intensities. Among the morphogenical characteristics of oats, only elongation rate of defoliate leaf differed between grazing intensities, with values of 0.059 and 0.081 cm/degree-day for low and high intensities, respectively. Grazing intensities did not alter structural characteristics of oats mixed with ryegrass and red clover. High grazing intensity enables maintenance of a higher number of ryegrass expanding leaves (1.7 leaves/tiller), thus it is suggested for management of pastures with oats mixed with Italian ryegrass and red-clover on intermittent grazing.<br>As características morfogênicas e estruturais de aveia-preta (Avena strigosa Schreb.) e azevém (Lolium multiflorum Lam.), em pastagem manejada sob duas intensidades de pastejo, foram quantificadas por meio da técnica de perfilhos marcados. As intensidades pretendidas de desaparecimento do valor da massa de forragem inicial foram 35% (baixa) e 65% (alta). Os animais experimentais foram ovinos e o intervalo entre pastejos foi determinado pela soma térmica de 300 graus-dia. O delineamento experimental foi inteiramente casualizado com duas intensidades de pastejo e duas repetições. As lâminas foliares de aveia e azevém foram removidas na proporção média de 57,5% do seu comprimento inicial em ambas as intensidades de pastejo. Entre as características morfogênicas da aveia, apenas a taxa de elongação de lâmina desfolhada diferiu entre as intensidades de pastejo, com valores de 0,059 e 0,081 cm/graus-dia para as intensidades alta e baixa, respectivamente. As intensidades de pastejo não provocaram alterações nas características estruturais da aveia em consorciação com azevém e trevo-vermelho. A intensidade de pastejo alta possibilita a manutenção de maior número de folhas em expansão de azevém (1,7 folhas/perfilho), portanto é recomendável para o manejo de pastagens da aveia em consórcio com azevém e trevo-vermelho sob pastejo intermitente