Performance evaluation study of ID RHD XT, a new genotyping assay for the detection of high-prevalence RhD negative and weak D types.

Background And Objectives: Routine serologic D typing does not distinguish between weak D subtypes and partial D phenotypes. The goal of this study was to validate the performance of the ID RHD XT genotyping assay.

Material And Methods: Previously serotyped samples for D antigen (n = 1000; 16% weak D serotyped donors) were analysed.

Performance evaluation study of ID CORE XT, a high throughput blood group genotyping platform.

Background: Traditionally, red blood cell antigens have been identified using serological methods, but recent advances in molecular biology have made the implementation of methods for genetic testing of most blood group antigens possible. The goal of this study was to validate the performance of the ID CORE XT blood group typing assay.

Materials And Methods: One thousand independent samples from donors, patients and neonates were collected from three research institutes in Spain and the Netherlands.

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).

A DNA microarray for the detection of point mutations and copy number variation causing familial hypercholesterolemia in Europe.

To facilitate genetic cascade screening for familial hypercholesterolemia (FH) in Europe, two versions (7 and 9) of a DNA microarray were developed to detect the most frequent point mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. The design of these microarrays is based on LIPOchip, version 4, which detects 191 LDLR and APOB mutations identified in Spanish patients with FH. A major improvement of LIPOchip, versions 7 and 9, is the ability to detect copy number variation (deletions or duplications of entire exons) in LDLR, thus abolishing the need to perform multiplex ligase-dependent probe amplification in patients with FH.

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.

Molecular characterization of familial hypercholesterolemia in Spain.

Familial hypercholesterolemia (FH), characterized by isolated elevation of plasmatic low-density lipoprotein (LDL) cholesterol and premature coronary heart disease (CHD), is associated with mutations in three major genes: LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin 9 (PCSK9). We have analyzed 5430 Spanish index cases and 2223 relatives since 2004 with LIPOchip(®) genetic diagnostic platform, a microarray for the detection of Spanish common mutations in these three genes, including copy number variation (CNV) in LDLR, followed by sequencing analysis of the coding regions of LDLR and exon 26 of APOB, when the result is negative. Samples were received from hospitals of all around Spain.

Functional characterization of splicing and ligand-binding domain variants in the LDL receptor.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder mostly caused by mutations in the LDLR gene. Although the detection of functional mutations in the LDLR gene provides an unequivocal diagnosis of the FH condition, there are many variants whose pathogenicity is still unknown. The aims of this study were to set up a rapid method to determine the effect of LDLR mutations, thereby providing an accurate diagnosis of FH, and to functionally characterize six LDLR mutations detected at high frequency by the LIPOchip(®) platform (Progenika Biopharma, Spain) in the Spanish population.

New contributions to the study of common double mutants in the human LDL receptor gene.

Variations in the gene encoding the low-density lipoprotein receptor (LDLR) can cause familial hypercholesterolemia (FH), one of the most common inherited metabolic disorders in humans. The functional effects of the p.Gln92Glu and p.

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.

Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis.

Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects.

Errors and reproducibility of DNA array-based detection of allelic variants in ADME genes: PHARMAchip.

Aims: Differences in adverse drug reactions can be explained by genetic variations, especially if they determine the expression of certain protein effectors and/or drug-metabolizing enzymes. Over the last decade, several tests screening for the most frequent polymorphisms in drug-metabolizing enzymes have been marketed for research and diagnostic purposes. The aim of this study was to assess the suitability of PHARMAchip for the genotyping of polymorphisms of genes associated with drug metabolism and response as an alternative to Jurilab Ltd's DrugMEt Test.

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.

HLA-DRB1*1501 and spinal cord magnetic resonance imaging lesions in multiple sclerosis.

Background: Multiple sclerosis (MS) is a heterogeneous neurologic disease with extensive variation with respect to the most affected central nervous system region (brain vs spinal cord).

Objective: To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined.

Design: Candidate gene study.

Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia.

Background And Objectives: Defects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH.

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Objectives: The aim of this study was to validate the Lipochip genetic diagnostic platform by assessing effectiveness, sensitivity, specificity and costs for the identification of patients with familial hypercholesterolemia (FH) in Spain. This platform includes the use of a DNA micro array, the detection of large gene rearrangements and the complete resequencing of the low-density lipoprotein receptor gene.

Design And Methods: DNA samples of patients with clinically diagnosed FH were analyzed for mutations by application of the Lipochip platform.

The Bloodgen Project of the European Union, 2003-2009.

The Bloodgen project was funded by the European Commission between 2003 and 2006, and involved academic blood centres, universities, and Progenika Biopharma S.A., a commercial supplier of genotyping platforms that incorporate glass arrays.