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Lina-Marcela Diaz-Gallo,
Luz María Medrano, María Gómez-García,
Carlos Cardeña,
Luis Rodrigo,
Juan Luis Mendoza,
Carlos Taxonera,
Antonio Nieto,
Guillermo Alcain,
Ignacio Cueto,
Miguel A López-Nevot,
Elena Urcelay,
Javier Martin
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ABSTRACT: The aim of this study was to evaluate the possible implication of CD24 gene in the genetic predisposition to inflammatory bowel disease (IBD). Our study population consisted of 1321 female Spanish individuals (369 Crohn's disease [CD] patients, 323 ulcerative colitis [UC] patients, and 629 healthy matched controls). Two putative functional polymorphisms, a C to T coding polymorphism (rs8734) and a TG deletion in the 3' untranslated region (rs3838646), were used as CD24 genetic markers and genotyped using a Taqman 5' allelic discrimination assay. The "del" allele of the dinucleotide deletion was associated with an increased risk of CD (odds ratio = 1.61, 95% confidence interval = 1.17-2.21, p(FDR) = 6.4E-03) but not with UC. Moreover, this allele was significant associated with the age of CD diagnosis between 17 and 40 years, the ileocolonic location, and the inflammatory behavior of CD. We observed no significant differences between the allelic or genotypic frequencies of the A57V polymorphism in our studied IBD cohort. Our results suggest that the rs3838646 CD24 polymorphism is part of the genetic background of CD.
Human immunology 06/2011; 72(10):969-72. · 2.55 Impact Factor
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[show abstract]
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ABSTRACT: A recent genome-wide association study (GWAS) of copy number variants (CNVs) in Crohn's disease (CD) confirmed association of three CNVs. The GWAS also provided evidence that a fourth CNV, CNVR7113.6, on chromosome 17 may alter susceptibility to CD (P = 0.0018). The aim of our study was to confirm the CNVR7113.6 association by genotyping two independent inflammatory bowel disease (IBD) cohorts and by conducting a subsequent meta-analysis.
In all, 1369 New Zealand Caucasians (489 CD patients, 463 ulcerative colitis [UC] patients, and 417 controls) and 2737 Spanish Caucasians (711 CD patients, 549 UC patients, and 1477 controls) were genotyped for a single nucleotide polymorphism (SNP), rs413778, in high linkage disequilibrium (r(2) = >0.99) with CNVR7113.6. Chi-square analysis was conducted to test for association of rs413778 with overall CD, UC, IBD, and with disease phenotype. New Zealand and Spanish genotypes were then combined with imputed rs413778 genotypes from the Wellcome Trust Case Control Consortium (WTCCC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) CD datasets to conduct a meta-analysis.
The minor allele of rs413778 conferred protection against CD in the Spanish cohort (CD: P = 0.004, odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.71-0.94). A similar, albeit nonsignificant protective effect was observed in New Zealand CD patients (P = 0.098, OR = 0.83, 95% CI: 0.66-1.04). No association with UC or disease phenotypes was detected in either cohort. Meta-analysis found significant cumulative evidence for a protective effect of rs413778 in Caucasian CD (P = 1.19E-05, OR = 0.86, 95% CI: 0.80-0.92).
This study provides the first independent replication of the association of CNVR7113.6 with CD.
Inflammatory Bowel Diseases 05/2011; 18(2):305-11. · 4.86 Impact Factor
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Rebecca L Roberts,
Jade E Hollis-Moffatt, María Gómez-García,
Karin Fransen,
Cyriel Y Ponsioen,
Bart A Crusius,
Cisca Wijmenga,
Javier Martín,
Rinse K Weersma,
Tony R Merriman,
Murray L Barclay,
Richard B Gearry,
Behrooz Z Alizadeh
Inflammatory Bowel Diseases 02/2011; 17(2):E19-21. · 4.86 Impact Factor
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Lina-Marcela Diaz-Gallo,
Laura Espino-Paisán,
Karin Fransen, María Gómez-García,
Suzanne van Sommeren,
Carlos Cardeña,
Luis Rodrigo,
Juan Luis Mendoza,
Carlos Taxonera,
Antonio Nieto, [......],
Adriaan A van Bodegraven,
Cisca Wijmenga,
Cyriel Y Ponsioen,
Richard B Gearry,
Rebecca L Roberts,
Rinse K Weersma,
Elena Urcelay,
Tony R Merriman,
Behrooz Z Alizadeh,
Javier Martin
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ABSTRACT: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism with both diseases.
A total of 1677 UC patients, 1903 CD patients, and 3111 healthy controls from an initial case-control set of Spanish Caucasian ancestry and two independent sample sets of European ancestry (Dutch and New Zealand) were included in the study. Genotyping was performed using TaqMan SNP assays for the R263Q (rs33996649) and R620W (rs2476601) PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD patients, 5695 UC patients, and 9254 controls to test the overall effect of the minor allele of R620W and R263Q polymorphisms.
The PTPN22 263Q loss-of-function variant showed initial evidence of association with UC in the Spanish cohort (P = 0.026, odds ratio [OR] = 0.61, 95% confidence interval [CI]: 0.39-0.95), which was confirmed in the meta-analysis (P = 0.013 pooled, OR = 0.69, 95% CI: 0.51-0.93). In contrast, the 263Q allele showed no association with CD (P = 0.22 pooled, OR = 1.16, 95% CI: 0.91-1.47). We found in the pooled analysis that the PTPN22 620W gain-of-function variant was associated with reduced risk of CD (P = 7.4E-06 pooled OR = 0.81, 95% CI: 0.75-0.89) but not of UC (P = 0.88 pooled, OR = 0.98, 95% CI: 0.85-1.15).
Our data suggest that two autoimmunity-associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated with UC, whereas the R620W was significantly associated with only CD.
Inflammatory Bowel Diseases 02/2011; 17(11):2287-94. · 4.86 Impact Factor
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ABSTRACT: Patients with Crohn's disease are at risk of developing osteoporosis, a disease in which the inflammatory process seems to be gaining importance. We performed a cross-sectional study to evaluate bone metabolism, osteoclastogenic factors [receptor activator of NF-kB ligand (RANK-L) and osteoprotegerin (OPG)] and soluble tumor necrosis factor-α receptor I (sTNF-RI) in patients with Crohn's disease and to correlate the findings with the degree of disease activity.
Sixty-four patients with Crohn's disease from the province of Granada (Spain) were included in this study. Bone mineral density (BMD) was studied through dual X-ray absorptiometry. Immunoassay was used to assess markers of bone formation [bone alkaline phosphatase (bALP) and osteocalcin (OC)] and bone resorption [tartrate resistant acid phosphatase (TRAP) and carboxyterminal telopeptide of type I procollagen (CTX)] as well as RANKL, OPG and sTNF-RI.
The percentage of patients with a Z-score ≤-2 in the femoral neck or lumbar spine was 20.3% and was higher in patients with active disease, although this difference was not significant. This percentage was only higher in patients receiving corticosteroids (11.1 vs. 9.1%; P=.001). Patients with the highest disease activity had higher TRAP levels. No significant differences were found in BMD but significant differences were found in TRAP levels with respect to C-reactive protein concentrations. No association was found between levels of OPG, RANKL and sTNF-RI and BMD or disease activity.
A substantial proportion of our patients had low BMD. Levels of bone turnover markers suggested higher bone resorption, possibly in relation to disease activity, without a compensatory increase in bone formation.
Gastroenterología y Hepatología 01/2011; 34(1):3-9. · 0.73 Impact Factor
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Lina-Marcela Diaz-Gallo,
Laura Espino-Paisán,
Karin Fransen,
Msc, María Gómez-García,
Suzanne Van Sommeren,
Carlos Cardeña,
Luis Rodrigo,
Juan Luis Mendoza,
Carlos Taxonera, [......],
Adriaan A Van Bodegraven,
Cisca Wijmenga,
Cyriel Y Ponsioen,
Richard B Gearry,
Rebecca L Roberts,
Rinse K Weersma,
Elena Urcelay,
Tony R Merriman,
Behrooz Z Alizadeh,
Javier Martin
[show abstract]
[hide abstract]
ABSTRACT: Background: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time
Inflammatory Bowel Diseases 01/2011; 17:2287-94. · 4.86 Impact Factor
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ABSTRACT: Inadequate serum levels of 25-hydroxyvitamin D (25OHD(3)) are deemed as a possible risk factor for osteoporosis in Crohn's disease (CD). Our aim is to determine the prevalence of inadequate serum levels of 25OHD(3) and its possible relationship with low bone mineral disease (BMD) in CD.
Sixty-four patients from the province of Granada (Spain) were enrolled. Serum levels of 25OHD3 and intact parathyroid hormone were measured. BMD was assessed by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN).
Almost 60% of patients showed inadequate serum levels of 25OHD(3), whereas only about 16% showed levels considered as adequate (≥30 ng/mL). Z-score at FN was ≤ -2 in 4.7% of patients and 20.3% at LS. Regarding T-score, 4.7 and 46.9% of patients met criteria for osteoporosis and osteopenia at FN, respectively, whereas 6.25 and 42.2% did it at LS, respectively. Patients with inadequate serum levels of 25OHD(3) had non-significant lower BMD, both at the LS and the FN.
Prevalence of inadequate serum levels of 25-(OH)D was high in our series. A no statistically-significant tendency towards low BMD in patients with inadequate serum levels of 25-(OH)D both at the FN and the LS was observed.
Medicina Clínica 12/2010; 137(2):62-5. · 1.38 Impact Factor
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Jezabel Varadé,
Rogelio Palomino-Morales,
Norberto Ortego-Centeno,
Manuel Díaz-Rubio,
Benjamín Fernández-Gutiérrez,
Miguel Ángel González-Gay,
Dora Pascual-Salcedo,
Alejandro Balsa,
Antonio Iglesias, María Gómez-García,
Torsten Witte,
Timothy R D J Radstake,
Marieke J H Coenen,
Elena Urcelay,
Javier Martín
Annals of the rheumatic diseases 09/2010; 70(4):711-2. · 8.11 Impact Factor
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Nieves Perdigones,
Ezequiel Martín,
Gema Robledo,
José Ramón Lamas,
Carlos Taxonera,
Manuel Díaz-Rubio,
Emilio G de la Concha,
Miguel Angel López-Nevot,
Antonio García, María Gómez-García,
Benjamín Fernández-Gutiérrez,
Javier Martín,
Elena Urcelay
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ABSTRACT: Chromosomal region 5p13 includes regulatory elements of the prostaglandin receptor EP4 (PTGER4) gene and is associated with inflammatory bowel disease (IBD) susceptibility. We aimed at corroborating the association of the PTGER4 risk variant in IBD. Given the proinflammatory activity of prostaglandin E(2) in rheumatoid arthritis (RA), the reduction in incidence and severity of collagen-induced arthritis observed in mice deficient in the prostaglandin receptor EP4, and a modest signal of association found in an RA genome-wide scan, we proposed to extend the investigation of this locus to RA patients. A total of 709 Crohn's disease (CD) patients, 662 ulcerative colitis (UC) patients, and 1369 control subjects were genotyped for rs17234657. This polymorphism was also analyzed in 605 RA patients, and rs6871834 was studied in the RA patient group. Replication of the previous finding in CD was achieved in our independent collections, although with a milder effect (odds ratios = 1.23) than that originally described. No further association of the previously mentioned polymorphisms was detected with either UC or RA patients. We validated this 5p13 signal as a genuine susceptibility factor for CD in Caucasian populations. Our data seem to rule out a major influence of these polymorphisms on UC or RA predisposition.
Human immunology 08/2010; 71(8):826-8. · 2.55 Impact Factor
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ABSTRACT: Recently, the signal transducer and activator of transcription 4 (STAT4) gene has been associated with multiple autoimmune diseases. Interestingly, a recent work showed that the T allele of the rs7574865 STAT4 SNP was associated with inflammatory bowel disease (IBD) in a Spanish population. The aim of the present study was to reevaluate the role of the STAT4 rs7574865 polymorphism on IBD. The present case-control study included 498 Crohn's disease (CD) patients, 402 ulcerative colitis (UC) patients, and 1296 healthy matched controls. Genotyping was performed using a PCR system with a pre-developed TaqMan allelic discrimination assay for the rs7574865 STAT4 SNP. Moreover, a meta-analysis was performed with the previous work in a Spanish population and the current study, including a final sample size of 1574 IBD patients (820 with CD and 754 with UC) and 2012 healthy controls. No evidence of association was found for the current case-control study (CD: p = 0.23, OR = 0.9, 95% CI = 0.75-1.1; UC: p = 0.17, OR = 1.14, 95% CI = 0.95-1.38). However, the meta-analysis showed that the STAT4 rs7574865 T allele was significantly associated with susceptibility to UC (p = 0.012 pooled; OR = 1.20, 95% CI = 1.04-1.39) but not CD (p = 0.71 pooled; OR = 0.93, 95% CI = 0.65-1.34). Our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for UC but not CD in the Spanish population.
Human immunology 02/2010; 71(5):515-9. · 2.55 Impact Factor
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Fiona Blanco-Kelly,
Fuencisla Matesanz,
Antonio Alcina,
María Teruel,
Lina M Díaz-Gallo, María Gómez-García,
Miguel A López-Nevot,
Luis Rodrigo,
Antonio Nieto,
Carlos Cardeña,
Guillermo Alcain,
Manuel Díaz-Rubio,
Emilio G de la Concha,
Oscar Fernandez,
Rafael Arroyo,
Javier Martín,
Elena Urcelay
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ABSTRACT: A functional polymorphism located at -1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions.
Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry.
The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01-1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06-1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93-1.17)].
The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.
PLoS ONE 01/2010; 5(7):e11520. · 4.09 Impact Factor
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Fiona Blanco-Kelly,
Fuencisla Matesanz,
Antonio Alcina,
María Teruel,
Lina M Díaz-Gallo, María Gómez-García,
Miguel A López-Nevot,
Luis Rodrigo,
Antonio Nieto,
Carlos Cardeña,
Guillermo Alcain,
Manuel Díaz-Rubio,
Emilio G de la Concha,
Oscar Fernandez,
Rafael Arroyo,
Javier Martín,
Elena Urcelay
PLoS ONE 01/2010; 5(8). · 4.09 Impact Factor
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Ana Márquez,
Gisela Orozco,
Alfonso Martínez,
Rogelio Palomino-Morales,
Miguel Fernández-Arquero,
Juan Luis Mendoza,
Carlos Taxonera,
Manuel Díaz-Rubio, María Gómez-García,
Antonio Nieto,
Miguel A López-Nevot,
Emilio G de la Concha,
Javier Martín,
Elena Urcelay
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ABSTRACT: Genome-wide association studies have reported the role of the interleukin (IL) 2-IL21 chromosomal region at 4q27 in several autoimmune conditions. Mice deficient in IL-2 develop a disease with clinical and histological similarity to ulcerative colitis (UC) in humans. Modest evidence of linkage with UC was tentatively proposed for the IL2 gene more than a decade ago. Therefore, we decide to investigate the association of polymorphisms in the IL-2 axis (IL2, IL2RA, and IL2RB genes) with inflammatory bowel diseases (IBDs).
Seven hundred and twenty-eight white Spanish unrelated IBD patients (356 Crohn's disease (CD) and 372 UC) and 549 ethnically matched controls were included in a case-control study. In addition, a Spanish replication cohort with 562 CD and 430 UC patients and 1,310 controls were analyzed. Eight single-nucleotide polymorphisms previously associated with different autoimmune diseases were analyzed using TaqMan chemistry.
The IL2-rs6822844 polymorphism modified CD predisposition (P=0.002; odds ratio, OR (95% confidence interval, CI)=0.61 (0.44-0.84)); this was replicated in the other Spanish cohort, resulting in a strong protective effect of the minor allele in the merged samples (P=0.0002; OR (95% CI)=0.70 (0.58-0.85)). A similar effect of rs6822844 was detected for UC. Another marker, rs11938795, also showed evidence of an association with CD (P=0.006; OR (95% CI)=0.73 (0.58-0.92)).
Polymorphisms within the IL2-IL21 linkage disequilibrium (LD) block show a novel association with IBD, this is concordant with suggestive previous results of whole genome analyses in CD and type 1 diabetes. Our data agree with the effect previously observed for other conditions and delineate a shared underlying mechanism.
The American Journal of Gastroenterology 06/2009; 104(8):1968-75. · 7.28 Impact Factor
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Ana Márquez,
Jezabel Varadé,
Gema Robledo,
Alfonso Martínez,
Juan Luis Mendoza,
Carlos Taxonera,
Miguel Fernández-Arquero,
Manuel Díaz-Rubio, María Gómez-García,
Miguel Angel López-Nevot,
Emilio G de la Concha,
Javier Martín,
Elena Urcelay
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ABSTRACT: Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn's disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2(-) vs NOD2(+) CD patients, G vs A: P=0.008; OR (95% CI)=1.54 (1.10-2.15); NOD2(-) CD patients vs controls: P=0.008; OR (95% CI)=1.37 (1.08-1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2(-) vs 204 NOD2(+) CD patients, G vs A: P=0.0012; OR(M-H) (95% CI)=1.49 (1.17-1.90); NOD2(-) CD patients vs controls: P=0.0007; OR(M-H) (95% CI)=1.35 (1.13-1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P=0.0005; OR (95% CI)=1.52 (1.19-1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.
European journal of human genetics: EJHG 05/2009; 17(10):1304-8. · 3.56 Impact Factor
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María Gómez-García,
Javier Oliver,
Ana Márquez,
Juan L Mendoza,
Miguel Angel López-Nevot,
Miguel Fernández-Arquero,
María F González-Escribano,
Manuel Díaz-Rubio,
Emilio G de la Concha,
Elena Urcelay,
Javier Martín,
Alfonso Martínez
[show abstract]
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ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Major histocompatibility complex (MHC) on the short arm of human chromosome 6 has been thoroughly studied as a susceptibility locus. However, one of the strongest MHC associations found, that of HLA-DR3 with UC protection, has not been observed in all populations. Our aim in the present study was to evaluate this negative association in a large cohort of Spanish UC patients and controls, and to try to elucidate which, if any, of the diverse DR3 haplotypes (identified by TNFa and b microsatellites, located in the MHC class III region) is most tightly associated (negatively) with the disease.
A total of 537 UC patients and 748 healthy controls from Spain were included in the present study. Low-resolution DR genotyping was performed by PCR and hybridization with allele-specific oligonucleotide probes. TNFa and b microsatellites were studied in a subset of samples (279 UC patients and 503 healthy controls) by PCR followed by capillary electrophoresis. DR-TNFa-TNFb haplotypes were estimated by the expectation-maximization algorithm and comparisons were performed by a chi2 test.
After a stepwise procedure, the only DR alleles significantly associated with the disease were DR3 (very strongly, protection) and DR4 (weakly, protection). The strong protective effect of DR3 was evenly distributed among the haplotypes DR3-TNFa1b5, DR3-TNFa2b3, and DR3-TNFother.
Our results confirm the strong protective effect of DR3 in our population, and suggest that the relevant protective gene is located centromeric to TNFa and TNFb markers in the MHC region.
The American Journal of Gastroenterology 01/2008; 102(12):2762-6. · 7.28 Impact Factor
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ABSTRACT: Recently, the interleukin 23 receptor (IL23R) gene encoding a subunit of the receptor of the inflammatory cytokine IL-23 has been identified as a novel genetic factor strongly associated with inflammatory bowel disease (IBD). We aimed to replicate the IBD association of IL23R genetic markers in an IBD independent Spanish cohort.
Four hundred sixty IBD patients of Spanish white origin (238 CD and 222 UC) and 342 ethnically matched healthy controls comprised the study population. Eight single nucleotide polymorphisms (SNPs) spanning the IL23R gene and its downstream intergenic region were selected as genetic markers and genotyped by using Taqman 5' allelic discrimination assay.
All genetic variants located within the IL23R gene were observed to confer a strong protective effect against IBD susceptibility in our population. The Arg381Gln (rs11209026) non-synonymous SNP was most significantly associated with IBD protection (odds ratio, 0.4; 95% confidence interval, 0.3-0.7). In addition to the single SNP analysis, we performed a haplotype analysis identifying 2 haplotypes significantly associated with IBD protection.
In this study we replicate the association of IL23R genetic variants with IBD in a Spanish population. These findings, together with the previous results, suggest that the IL23R gene is one of the genetic factors implicated in the genetics of IBD in the general population.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 08/2007; 5(8):977-81, 981.e1-2. · 5.64 Impact Factor
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Concepción Núñez,
Javier Oliver,
Juan Luis Mendoza, María Gómez-García,
Carlos Taxonera,
Luis M Gómez,
Miguel A López-Nevot,
Emilio G de la Concha,
Elena Urcelay,
Alfonso Martínez,
Javier Martín
[show abstract]
[hide abstract]
ABSTRACT: The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility.
We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using chi2 tests.
No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04-3.02, vs. controls).
A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary.
BMC Medical Genetics 02/2007; 8:75. · 2.33 Impact Factor
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Concepción Núñez,
Javier Oliver,
Juan Mendoza, María Gómez-García,
Carlos Taxonera,
Luis Gómez,
Miguel López-Nevot,
de la Concha Emilio,
Elena Urcelay,
Alfonso Martínez,
Javier Martín
[show abstract]
[hide abstract]
ABSTRACT: Abstract
Background
The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility.
Methods
We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ<sup>2 </sup>tests.
Results
No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209 _G allele could increase susceptibility in the subgroup of HLA-DR3 -positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, vs. controls).
Conclusion
A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3 -positive individuals but further studies are necessary.
BMC Medical Genetics. 01/2007;
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ABSTRACT: This study investigated the influence of the NFKB1-94ins/delATTG in the susceptibility/phenotype to ulcerative colitis.
We analyzed the distribution of -94ins/delATTG NFKB1 in 258 patients and 264 healthy controls from southern Spain by a polymerase chain reaction-fluorescent method.
The genotype and allele frequencies of -94ins/delATTG did not significantly differ between patients and controls. In fact, the frequency of the -94delATTG allele was almost identical in both groups (34.8% and 35.4%, respectively), and the del/del genotype was underrepresented in UC patients (11.2% versus 14%). In addition, no association of this polymorphism was found with any of the clinical parameters analyzed.
These results suggest that the NFKB1 -94ins/delATTG gene variation, previously associated with UC susceptibility in North Americans, does not influence either susceptibility or phenotype of UC in the Spanish population.
Inflammatory Bowel Diseases 07/2005; 11(6):576-9. · 4.86 Impact Factor
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Concepción Núñez,
Francisco Javier Oliver,
Juan L Mendoza, María Gómez-García,
Carlos Taxonera,
Luis M Gómez,
M A López-Nevot,
Emilio G de la Concha,
Elena Urcelay,
Alfonso Martínez,
Javier Martín Ibáñez
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ABSTRACT: This article is available from: http://www.biomedcentral.com/1471-2350/8/75 [Background] The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility. [Methods] We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ2 tests. [Results] No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, vs. controls). [Conclusion] A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary. This work was supported by grants SAF2003-08522 and SAF2006-00398. Concepción Núñez and Alfonso Martínez have a FIS contract (CA06/0163 and CP04/00175, respectively) and Elena Urcelay works for the "Fundación para la Investigación Biomédica-Hospital Clínico San Carlos". Peer reviewed
