Derio, Spain
Derio, Spain

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Ruiz J.R.,Karolinska Institutet | Buxens A.,Progenika Biopharma | Artieda M.,Progenika Biopharma | Arteta D.,Progenika Biopharma | And 5 more authors.
Journal of Science and Medicine in Sport | Year: 2010

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= 0.030) and G allele (P= 0.026) was higher in the power athletes group compared with the control group. The frequency of the GG genotype (P= 0.033) and G allele (P= 0.013) was also higher in the power athletes group compared with the endurance athletes group. The odds ratio of being a power athlete if the subject had the GG genotype (dominant model) was 2.471 (95% confidence interval: 1.242-4.915) compared to the control group or the endurance athlete group. We did not find differences between the control and endurance athlete groups. In summary, our findings suggest that the G allele of the IL6-174 G/C polymorphism might favour sprint/power sports performance. © 2009 Sports Medicine Australia.


Gomez-Gallego F.,European University at Madrid | Ruiz J.R.,Karolinska Institutet | Buxens A.,Progenika Biopharma | Altmae S.,Karolinska University Hospital | And 10 more authors.
Physiological Genomics | Year: 2010

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. We computed a health-related total genotype score (TGS, 0-100) from the accumulated combination of the 33 variants. We did not observe significant differences in genotype or allele distributions among groups, except for the rs4994 polymorphism (P < 0.001). The computed health-related TGS was similar among groups (23.8 ± 1.0 vs. 24.2 ± 0.8 in control subjects and athletes, respectively; P = 0.553). Similar results were obtained when computing specific TGSs for each main disease category (cardiovascular disease and cancer). We observed no evidence that male elite endurance athletes are genetically predisposed to have lower disease risk than matched nonathletic control subjects. Copyright © 2010 American Physiological Society.


Ruiz J.R.,University of Granada | Ruiz J.R.,Karolinska Institutet | Fiuza-Luces C.,European University at Madrid | Buxens A.,Progenika Biopharma | And 8 more authors.
Age | Year: 2012

Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n=54, 100-108 years, 48 women) and (ii) ethnically matched healthy controls (n = 87, 19-43 years, 47 women). We computed a 'global' genotype score (GS) for 62 genetic variants (mutations/ polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The 'global' GS was similar among groups (centenarians: 31.0±0.6; controls 32.0±0.5, P=0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P<0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group differences in the frequency of GSTTl and GSTMl (presence/absence) genotypes after adjusting for multiple comparisons. The likelihood of having the GSTTl low-risk (functional) allele was higher in centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810-13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868-1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTTl, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings. © American Aging Association 2011.


PubMed | University of Amsterdam, University of Washington, University of Cologne, University of Marburg and 11 more.
Type: Journal Article | Journal: Journal of clinical lipidology | Year: 2016

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.We used gene sequencing followed by in-vivo/in-vitro and in-silico tools for classification. We classified 125 rare LPL mutations in 33 subjects thought to have LPL deficiency and in 314 subjects selected for very SHTG.Of the 33 patients thought to have LPL deficiency, only 13 were homozygous or compound heterozygous for deleterious mutations in the LPL gene. Among the 314 very SHTG patients, 3 were compound heterozygous for pathogenic mutants. In a third group of 51,467 subjects, from a general population, carriers of common variants, Asp9Asn and Asn291Ser, were associated with mild increase in triglyceride levels (11%-35%).In total, 39% of patients clinically diagnosed as LPL deficient had 2 deleterious variants. Three patients selected for very SHTG had LPL deficiency. The deleterious mutations associated with LPL deficiency will assist in the diagnosis and selection of patients as candidates for the presently approved LPL gene therapy.


Cleynen I.,Catholic University of Leuven | Gonzalez J.R.,Hospital Clinic i Provincial IDIBAPS | Figueroa C.,Hospital Clinic i Provincial IDIBAPS | Franke A.,University of Kiel | And 19 more authors.
Gut | Year: 2013

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. CD outcomes of interest were ileal (L1), colonic (L2) and ileocolonic disease location (L3); stenosing (B2) or penetrating behaviour (B3); perianal disease; extraintestinal manifestations; and bowel resection. A complicated disease course was defined as stenosing or penetrating behaviour, perianal disease and/or bowel resection. Association between CD-SNPs or patient characteristics and specified outcomes was studied. Results: Several CD-SNPs and clinical characteristics were statistically associated with outcomes of interest. The NOD2 gene was the most important genetic factor, being an independent predictive factor for ileal location (p=2.02×10-06, OR=1.90), stenosing (p=3.16×10 -06, OR=1.82) and penetrating (p=1.26×10-02, OR=1.25) CD behaviours, and need for surgery (p=2.28×e-05, OR=1.73), and as such was also the strongest factor associated with a complicated disease course (p=6.86×10-06, OR=2.96). Immunomodulator (azathioprine/6-mercaptopurine and methotrexate) use within 3 years after diagnosis led to a reduction in bowel stenoses (p=1.48×10-06, OR=0.35) and surgical rate (p=1.71×10-07, OR=0.34). Association between each outcome and genetic scores, created using significant SNPs in the univariate analysis, revealed large differences in the probability of developing fistulising disease (IL23R, LOC441108, PRDM1, NOD2; p=9.64e-4, HR=1.43), need for surgery (IRGM, TNFSF15, C13ORF31, NOD2; p=7.12×10-03, HR=1.35), and stenosing disease (NOD2, JAK2, ATG16L1; p=3.01×10 -02, HR=1.29) among patients with low and high score. Conclusions: This large multicentre cohort study has found several genetic and clinical factors influencing the clinical course of CD. NOD2 and early immunomodulator use are the clinically most meaningful predictors for its clinical course.


Fresquet V.,University of Navarra | Robles E.F.,University of Navarra | Parker A.,Royal Bournemouth Hospital | Martinez-Useros J.,University of Navarra | And 16 more authors.
British Journal of Haematology | Year: 2012

Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Deletion or uniparental disomy of chromosome 7q were detected in 42 of 114 (37%) SMZLs but in only nine of 170 (5%) mature B-cell lymphomas (P < 0·00001). The presence of unmutated IGHV, genomic complexity, 17p13-TP53 deletion and 8q-MYC gain, but not 7q deletion, correlated with shorter overall survival of SMZL patients. Mapping studies narrowed down a commonly deleted region of 2·7 Mb in 7q32.1-q32.2 spanning a region between the SND1 and COPG2 genes. High-throughput sequencing analysis of the 7q32-deleted segment did not identify biallelic deletions/insertions or clear pathogenic gene mutations, but detected six nucleotide changes in IRF5 (n = 2), TMEM209 (n = 2), CALU (n = 1) and ZC3HC1 (n = 1) not found in healthy individuals. Comparative expression analysis found a fourfold down-regulation of IRF5 gene in lymphomas with 7q32 deletion versus non-deleted tumours (P = 0·032). Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased proliferation and increased apoptosis in vitro, and impaired lymphoma development in vivo. These results show that cryptic deletions, insertions and/or point mutations inactivating genes within 7q32 are not common in SMZL, and suggest that IRF5 may be a haploinsufficient tumour suppressor in this lymphoma entity. © 2012 Blackwell Publishing Ltd.


Buxens A.,Progenika Biopharma | Ruiz J.R.,Karolinska Institutet | Arteta D.,Progenika Biopharma | Artieda M.,Progenika Biopharma | And 7 more authors.
Scandinavian Journal of Medicine and Science in Sports | Year: 2011

The goal of our study was to discriminate potential genetic differences between humans who are in both endpoints of the sports performance continuum (i.e. world-class endurance vs power athletes). We used DNA-microarray technology that included 36 genetic variants (within 20 different genes) to compare the genetic profile obtained in two cohorts of world-class endurance (N=100) and power male athletes (N=53) of the same ethnic origin. Stepwise multivariate logistic regression showed that the rs1800795 (IL6-174 G/C), rs1208 (NAT2 K268R) and rs2070744 (NOS3-786 T/C) polymorphisms significantly predicted sport performance (model χ 2=25.3, df=3, P-value <0.001). Receiver-operating characteristic (ROC) curve analysis showed a significant discriminating accuracy of the model, with an area under the ROC curve of 0.72 (95% confidence interval: 0.66-0.81). The contribution of the studied genetic factors to sports performance was 21.4%. In summary, although an individual's potential for excelling in endurance or power sports can be partly predicted based on specific genetic variants (many of which remain to be identified), the contribution of complex gene-gene interactions, environmental factors and epigenetic mechanisms are also important contributors to the "complex trait" of being an athletic champion. Such trait is likely not reducible to defined genetic polymorphisms. © 2010 John Wiley & Sons A/S.


Santiago C.,European University at Madrid | Ruiz J.R.,Karolinska Institutet | Buxens A.,Progenika Biopharma | Artieda M.,Progenika Biopharma | And 7 more authors.
British Journal of Sports Medicine | Year: 2011

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=0.001). Heterozygosity for the ADRB3 Trp64Arg polymorphism seems to be associated with elite endurance performance, while other variants of the β-adrenergic receptors' genes do not seem to significantly influence top-level sports performance, at least in athletes of Spanish origin.


Ruiz J.R.,Karolinska Institutet | Arteta D.,Karolinska Institutet | Buxens A.,Progenika Biopharma | Artieda M.,Progenika Biopharma | And 5 more authors.
Journal of Applied Physiology | Year: 2010

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). We analyzed six polymorphism that are candidates to explain individual variations in elite power athletic status or power phenotypes (ACE I/D, ACTN3 R577X, AG7/Met235Thr, GDF-8 K153R, IL6 -174 G/C, and NOS3 -786T>C) in 53 elite track and field power athletes (jumpers, sprinters), 100 nonathletic controls, and 100 elite endurance athletes (distance runners and road cyclists) (all Spanish Caucasian males). The mean TGS was significantly higher in power athletes (70.8 ± 17.3) compared with endurance athletes (60.4 ± 15.9; P < 0.001) and controls (63.3 ± 13.2; P = 0.012), whereas it did not differ between the latter two groups (P = 0.366). A total of five power athletes (9.4%, all sprinters) had a theoretically "optimal" TGS of 100 vs. 0 subjects in the other two groups. The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the six candidate polymorphisms we studied was very small, i.e., ∼0.2% (or 1 in 500 Spanish individuals). We have identified a polygenic profile that allows us, at least partly, to distinguish elite power athletes from both endurance athletes and nonathletic population. Copyright © 2010 the American Physiological Society.


Trademark
Progenika Biopharma | Date: 2015-08-13

Chemical reagents and diagnostic preparations other than for medical or veterinary use; chemicals used in industry, science, photography, horticulture and forestry excluding fungicides, herbicides, insecticides and parasiticides; unprocessed artificial resins; soil fertilizers; fire extinguishing compositions; tempering and soldering preparations; chemicals for preserving foodstuffs; tanning substances for use in leather manufacturing; adhesives for use in industry. Chemical reagents and diagnostic preparations for medical or veterinary purposes; sanitary preparations for medical use; analgesics; food for babies; poultices and materials for dressings, namely, gauze, wadding, bandages, adhesive plasters; disinfectants for hygiene purposes; preparations for destroying vermin; fungicides, herbicides. Scientific research services for medical and veterinary purposes; research, development and scientific consultancy services in the field of biomedicine and cell culture engineering; research and development of new products; research and development of chemical reagents and diagnostic products for medical and veterinary use; bacteriological, viral, biological and chemical research services; chemical analysis services; scientific and technological services, namely, research and design services in the field of chemical reagents; industrial analysis and research services in the field of chemical reagents.

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