A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes

Period of incubation and posthatching holding time influence on broiler performance

The present study had the objective of investigating the performance of broilers housed immediately after hatching or after a 12 or 24 hour of post-hatching holding time. One thousand and six hundred male Ross 308 broiler chicks with an initial body weight of 46 grams were used. These chicks were distributed in a completely randomized experimental design with 5 treatments and 8 replications of 35 birds in each treatment. The treatments in this study consisted of the removal of chicks from the hatchery in three different times: after 480, 492 and 504 hours of incubation. In each one of these times, 280 chicks were removed from the hatchery and immediately housed. Another group of an identical number of chicks of each time remained in the hatchery to be housed at 504 hours after hatching. The chick group corresponding to those hatched at 480 and 492 hours performed better until 7 days. However, no differences in body weight or body weight gain were observed at the end of the study. Feed efficiency, however was worse for the birds hatched and placed at 480 hours. There were no differences among treatments for mortality

Performance of broilers fed increased levels energy in the pre-starter diet and on subsequent feeding programs having with acidulated soybean soapstock supplementation

This study aimed to evaluate broiler responses to increases in feed energy (2,870, 3,000 and 3,100 kcal ME/kg) and the inclusion of Acidulated Soybean Soapstock (ASS) when compared to Degummed Soybean Oil (DSO) in feeds from placement to 7 days of age. From 7 to 42 days ASS or DSO were included in diets that contained similar energy and nutrient levels. Metabolizable energy values used to formulate the diets for ASS and DSO were 8,351 and 7,701 kcal ME/kg in the first week and 9,314 and 8,559 kcal ME/kg afterwards, respectively. Diets were based on corn and soybean meal and were fed to 1,600 one-d-old male broiler chicks randomly placed in 40 floor pens. No differences in performance due to fat source were seen at 7 days. However, the increase in energy levels to 3,100 kcal ME/kg reduced feed intake, whereas feed conversion was improved with energy at 3,000 kcal ME/kg. Live performance, and the yields of carcass and commercial cuts were not affected by the type of fat included in the feeds from 7 to 42 days, except for increased body weight at 21 and 35 days with ASS supplementation. Litter moisture at 7, 21, 35 and 42 days was not affected by any of the factors and there were no residual effects of treatments at 21, 35 and 42 days of age. On the other hand, body weight at 35 days was affected by the interaction of diets fed in the first week with those provided afterwards. The results showed that ME values used for DSO and ASS are adequate and that ASS may be used as fat source in broiler feeds from placement to 42 days of age

Associations of non-Hodgkin lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci

Autoimmune conditions and immune system–related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988–2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).16 page(s