A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.

Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial.

Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study.

Objective: The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients.

Methods: This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included.

Candidate's single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis.

The objective of this study is to identify single-nucleotide polymorphisms (SNPs) predictors of treatment nonresponse to the first anti-TNF-alpha agent in ankylosing spondylitis (AS). Patients were classified as "nonresponders" if they failed to achieve improvement ≥50 % of the initial BASDAI. We selected candidate SNPs previously reported, associated with susceptibility or pathogenesis of AS and with other spondylarthropaties (SpAs).

Both baseline clinical factors and genetic polymorphisms influence the development of severe functional status in ankylosing spondylitis.

Functional severity in ankylosing spondylitis (AS) patients is variable and difficult to predict early. The aim of our study was to assess whether a combination of baseline clinical factors and genetic markers may predict the development of severe functional status in AS. We performed a cross-sectional association study on AS patients included in the Spanish National Registry of Spondyloarthropathies--REGISPONSER.

Genetic polymorphisms inside and outside the MHC improve prediction of AS radiographic severity in addition to clinical variables.

Objective: The aim of this study was to analyse if single nucleotide polymorphisms (SNPs) inside and outside the MHC region might improve the prediction of radiographic severity in AS.

Methods: A cross-sectional multi-centre study was performed including 473 Spanish AS patients previously diagnosed with AS following the Modified New York Criteria and with at least 10 years of follow-up from the first symptoms of AS. Clinical variables and 384 SNPs were analysed to predict radiographic severity [BASRI-total (BASRI-t) corrected for the duration of AS since first symptoms] using multivariate forward logistic regression.

ERAP1 polymorphisms and haplotypes are associated with ankylosing spondylitis susceptibility and functional severity in a Spanish population.

Objectives: The aim of this study was to assess the involvement of the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene in AS susceptibility and functional severity in a Spanish population.

Methods: Eight single nucleotide polymorphisms (SNPs) spanning the ERAP1 gene were genotyped by allele-specific fluorescent PCR in 300 AS Spanish patients and 300 spondylarthritis-free controls. The influence of the ERAP1 SNPs on the functional severity of AS was analysed with the BASFI corrected for disease duration.

Biphasic adaptative responses in VLDL metabolism and lipoprotein homeostasis during Gram-negative endotoxemia.

Dyslipidemia and hepatic overproduction of very low density lipoprotein (VLDL) are hallmarks of the septic response, yet the underlying mechanisms are not fully defined. We evaluated the lipoprotein subclasses profile and hepatic VLDL assembly machinery over 24 h in fasted LPS-treated rats. The response of serum non-esterified fatty acids (NEFA) and glucose to endotoxin was biphasic, with increased levels of NEFA and hypoglycemia in the first 12 h-phase, and low NEFA and high glucose in the second 12 h-phase.

Association of the intergenic single-nucleotide polymorphism rs10865331 (2p15) with ankylosing spondylitis in a Spanish population.

Objective: A recent genome-wide association study has identified 2 single-nucleotide polymorphisms (SNP) associated with ankylosing spondylitis (AS), rs10865331 (2p15) and rs2242944 (21q22). We assessed the association of these SNP with AS in a Spanish population.

Methods: Four hundred fifty-six patients with AS fulfilling the modified New York Criteria and 300 healthy donors were analyzed.

Kupffer cell products and interleukin 1beta directly promote VLDL secretion and apoB mRNA up-regulation in rodent hepatocytes.

Plasma VLDL accumulation in Gram-negative sepsis is partly ascribed to an increased hepatic VLDL production driven by pro-inflammatory cytokines. We previously showed that hepatocytes of the Kupffer cell (KC)-rich periportal area are major contributors to enhanced VLDL production in lipopolysaccharide (LPS)-injected rats. However, it remains to be established whether KC generated products directly affect the number (apoB) and composition of secreted VLDL.

Upregulation of apolipoprotein B secretion, but not lipid, by tumor necrosis factor-alpha in rat hepatocyte cultures in the absence of extracellular fatty acids.

Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the host response to infection. Rapidly liberated to the bloodstream, TNF-alpha triggers the production of other cytokines and the acute-phase response. Hypertriglyceridemia is a sepsis hallmark associated with high plasma levels of very low-density lipoprotein (VLDL) particles, partly ascribed to increased hepatic production.

Isolation and characterization of the rat SND p102 gene promoter: putative role for nuclear factor-Y in regulation of transcription.

In this work, we report the isolation and characterization of a 1,688-bp sequence corresponding to the promoter region of the rat endoplasmic reticulum (ER) cholesterol ester hydrolase gene, renamed as staphylococcal nuclease domain-containing protein of 102 kDa (SND p102) in GenBank database according to the structural properties and molecular weight of the protein. The transcription start site was located 216 bases upstream of the ATG start codon by RNA ligase mediated-rapid amplification of cDNA ends (RLM-RACE). Bioinformatic analysis of the isolated sequence revealed a lack of typical promoter TATA box and the presence of GC-rich motifs and CCAAT boxes recognized by Sp 1 and nuclear factor-Y among other putative binding sites for a number of transcription factors implicated in both basal and regulated processes.