Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency.

Background: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight into the deleterious effect of the mutations is clinically essential.

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).

Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease.

Objective: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions.

Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project.

Objective: Through genome-wide association scans and meta-analyses thereof, over 70 genetic loci (Crohn's disease (CD) single nucleotide polymorphisms (SNPs)) are significantly associated with CD. We aimed to investigate the influence of CD-SNPs and basic patient characteristics on CD clinical course, and develop statistical models to predict CD clinical course.

Design: This retrospective study included 1528 patients with CD with more than 10 years of follow-up from eight European referral hospitals.

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 predisposition to early recurrence in clinically localized prostate cancer.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Currently available nomograms to predict preoperative risk of early biochemical recurrence (EBCR) after radical prostatectomy are solely based on classic clinicopathological variables. Despite providing useful predictions, these models are not perfect. Indeed, most researchers agree that nomograms can be improved by incorporating novel biomarkers.

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.

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.

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

Purpose: Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy.

Materials And Methods: We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery.

Can we identify a power-oriented polygenic profile?

Using the model originally developed by Williams and Folland (J Physiol 586: 113-121, 2008), we determined 1) a "total genotype score" (TGS, from the accumulated combination of the 6 polymorphisms, with a maximum value of "100" for the theoretically optimal polygenic score) in a group of elite power athletes, endurance athletes, and nonathletic controls, and 2) the probability for the occurrence of Spanish individuals with the "perfect" power-oriented profile (i.e., TGS = 100).

Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms.

Objective: To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs).

Methods: We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray.

Are elite endurance athletes genetically predisposed to lower disease risk?

We compared a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among nonathletic healthy control subjects and elite endurance athletes. The study sample comprised 100 healthy Spanish male nonathletic (sedentary) control subjects and 100 male elite endurance athletes. We analyzed 33 disease risk-related mutations and polymorphisms.

The -174 G/C polymorphism of the IL6 gene is associated with elite power performance.

The -174 G/C polymorphism [rs1800795] of the IL6 gene is a candidate to explain individual variations in health and exercise related phenotypes. We compared -174 G/C genotypic and allelic frequencies in three groups of men of the same Caucasian (Spanish) descent: elite endurance athletes (cyclists, runners; n=100); elite power athletes (jumpers, throwers, sprinters; n=53) and non-athletic controls (n=100). The frequency of the GG genotype (P=0.

The -786 T/C polymorphism of the NOS3 gene is associated with elite performance in power sports.

The NOS3 gene is a candidate to explain individual variations in health and exercise related phenotypes. We compared genotypic and allelic frequencies of the NOS3 -786 T/C polymorphism (rs2070744) in three groups of men of the same Caucasian (Spanish) descent: (i) elite endurance athletes (cyclists, runners; N = 100); (ii) elite power athletes (jumpers, throwers, sprinters; N = 53) and (iii) non-athletic controls (N = 100). The frequency of the TT genotype was significantly higher in power athletes (57%) than in the endurance (33%, P = 0.

Trp64Arg polymorphism in ADRB3 gene is associated with elite endurance performance.

In this study, allele and genotype frequencies of the ADRB1 Arg389Gly (rs1801253), ADRB2 Gly16Arg (rs1042713) and Gln27Glu (rs1042714), and ADRB3 Trp64Arg (rs4994) variations were compared in the following three groups of Spanish (Caucasian) men: (1) world-class endurance athletes (E; runners and cyclists, n=100), (2) elite power athletes (P; sprinters, jumpers and throwers, n=53) and (3) non-athletic controls (C; n=100). No significant differences were observed in genotype and allele distributions among the study groups except for the ADRB3 Trp64Arg polymorphism in E versus C (27% vs 8% of carriers of the Arg allele in E and C, p<0.001; frequency of the minor Arg (C) allele of 14% vs 4% in E and C, p=0.

Association and linkage disequilibrium analyses of APOE polymorphisms in atherosclerosis.

Background: Apolipoprotein E (apo E) plays a major role in lipid metabolism, and its genetic variations have been associated with cardiovascular risk. The objective of this study was to investigate the influence of the APOE promoter (-491 A/T, -427 T/C and -219 G/T) and coding region (APOE epsilon2/epsilon3/epsilon4) polymorphisms in atherosclerosis disease by association and linkage disequilibrium analyses.

Materials And Methods: We analyzed these polymorphisms in a sample of 286 subjects with atherosclerosis disease: 153 subjects with atherothrombotic stroke (ATS) and 133 subjects with ischemic heart disease (IHD); and in two control groups, 103 newborns and 114 elderly subjects.

Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response.

Background: Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL.

Ultrasonography for the evaluation of visceral fat and the metabolic syndrome.

Association between abdominal obesity and cardiovascular disease has been related with visceral adiposity, through the predisposition of developing type 2 diabetes mellitus and metabolic syndrome (MS). Sonography is a simple and reliable method to measure both subcutaneous and visceral fat. To analyze the relationship of anthropometric measurements with abdominal adiposity measured by sonography and to analyze the utility of sonography in the prediction of insulin resistance (IR) and the other components of MS.

Tendon xanthomas in familial hypercholesterolemia are associated with a differential inflammatory response of macrophages to oxidized LDL.

Tendon xanthomas (TX) are pathognomonic lipid deposits commonly found in familial hypercholesterolemia (FH) patients. The aim of this study was to determine whether macrophages from FH patients with TX (TX+) have higher predisposition to foam cells formation after oxidized LDL (oxLDL) overload than those from FH patients without TX (TX-), and if their differential gene expression profile could explain these different phenotypes. Total RNA pools from macrophages from FH patients TX+ and TX- were analyzed using Affymetrix oligonucleotide arrays to evaluate the gene expression profile in presence and absence of oxLDL.