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ABSTRACT: OBJECTIVE: To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA). METHOD: RA patients were selected from a group of subjects genotyped for the rs8192284 SNP, located at the proteolytic cleavage site of IL-6R. sIL6R and protease levels (ADAM17) were measured and the contribution of alternative splicing in the generation of sIL-6R was evaluated through qRT-PCR. RESULT: Increased sIL-6R plasma levels and expression of spliced isoform generating sIL-6R are genotype dependent. ADAM17 concentrations were independent of the genotype studied. CONCLUSION: Alternative splicing and proteolytic cleavage participate in sIL-6R generation in RA. The rs8192284 polymorphism determines the sIL-6R plasma level through differential proteolytic rupture controlled by ADAM17.
Cytokine 01/2013; · 3.02 Impact Factor
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Aurora Serrano,
F David Carmona,
Santos Castañeda,
Roser Solans,
José Hernández-Rodríguez,
María C Cid,
Sergio Prieto-González,
José A Miranda-Filloy, Luis Rodríguez-Rodríguez,
Inmaculada C Morado, [......],
Ainhoa Unzurrunzaga,
Begoña Marí-Alfonso,
Julio Sánchez-Martín,
María Jesús García-Villanueva,
Ana Hidalgo-Conde,
Giulia Pazzola,
Luigi Boiardi,
Carlo Salvarani,
Miguel A González-Gay,
Javier Martín
Annals of the rheumatic diseases 12/2012; · 8.11 Impact Factor
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F David Carmona,
Aurora Serrano, Luis Rodríguez-Rodríguez,
José Luis Callejas,
Carmen P Simeón,
Patricia Carreira,
Santos Castañeda,
Roser Solans,
Ricardo Blanco,
Miguel A González-Gay,
Javier Martín
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ABSTRACT: We evaluated whether a single-nucleotide polymorphism (SNP) of the TRAF6 gene previously associated with systemic lupus erythematosus and rheumatoid arthritis may be a common risk factor for systemic sclerosis (SSc) and giant cell arteritis (GCA).
A total of 1185 patients with SSc, 479 patients with biopsy-proven GCA, and 1442 unrelated healthy controls of white Spanish origin were genotyped for the rs540386 variant using a specifically designed TaqMan(©) allele discrimination assay.
No significant associations of this SNP with global SSc or GCA were found. This was also the case when the potential associations of the TRAF6 polymorphism with the main clinical phenotypes of the 2 diseases (e.g., limited cutaneous and diffuse cutaneous SSc, or presence of polymyalgia rheumatica and visual ischemic manifestations in GCA) were assessed.
Our data do not support a role of the rs540386 TRAF6 variant as a key component of the genetic network underlying SSc and GCA.
The Journal of Rheumatology 05/2012; 39(6):1275-9. · 3.69 Impact Factor
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Aurora Serrano,
F David Carmona,
José A Miranda-Filloy,
Santos Castañeda, Luis Rodríguez-Rodríguez,
Inmaculada C Morado,
Carmen Gómez-Vaquero,
Roser Solans,
Bernardo Sopeña,
Ricardo Blanco,
Ainhoa Unzurrunzaga,
Norberto Ortego-Centeno,
Begoña Marí-Alfonso,
Eugenio de Miguel,
Ana Hidalgo-Conde,
Javier Martín,
Miguel A González-Gay
[show abstract]
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ABSTRACT: CD226 genetic variants have been associated with a number of autoimmune diseases. The aim of this study was to investigate the potential implication of the CD226 loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA).
A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven GCA and 1414 healthy controls were included in the study. Three CD226 polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses.
No significant association between the CD226 polymorphisms and susceptibility to GCA was found (rs727088: p=0.92, OR=1.01, CI 95% 0.86-1.18; rs34794968: p=0.61, OR=1.04, CI 95% 0.89-1.22; rs763361: p=0.88, OR=0.99, CI 95% 0.84-1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the clinical manifestations of the disease.
Our results show that the three CD226 polymorphisms analysed do not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis.
Clinical and experimental rheumatology 03/2012; 30(1 Suppl 70):S29-33. · 2.15 Impact Factor
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ABSTRACT: Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.
Mediators of Inflammation 01/2012; 2012:574817. · 3.26 Impact Factor
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F David Carmona,
Aurora Serrano, Luis Rodríguez-Rodríguez,
Santos Castañeda,
José A Miranda-Filloy,
Inmaculada C Morado,
Javier Narváez,
Roser Solans,
Bernardo Sopeña,
Begoña Marí-Alfonso,
Ainhoa Unzurrunzaga,
Norberto Ortego-Centeno,
Ricardo Blanco,
Eugenio de Miguel,
Ana Hidalgo-Conde,
Javier Martín,
Miguel A González-Gay
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether a functional integrin alpha M (ITGAM) variant is involved in susceptibility to and clinical manifestations of giant cell arteritis (GCA).
A Spanish cohort of 437 white patients with biopsy-proven GCA and 1388 healthy controls were genotyped using the TaqMan allele discrimination technology.
No association was observed between ITGAM rs1143679 and GCA (p = 0.80, OR 0.97). Similarly, subphenotype analyses did not yield significant differences between the case subgroups and the control set or between GCA patients with or without the main specific features of GCA.
Our results suggest that the ITGAM rs1143679 variant does not play an important role in the pathophysiology of GCA.
The Journal of Rheumatology 10/2011; 38(12):2598-601. · 3.69 Impact Factor
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ABSTRACT: To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO. Genotyping of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 and signal transducers and activators of transcription 4 (STAT4) rs7574865 polymorphism was performed using fast real-time PCR System. Shared epitope, antibodies directed against cyclic citrulinated peptide (anti-CCP) antibodies and a higher level of education were associated with a younger age at disease onset (P = 0.033, P = 0.004 and P < 0.0001, respectively). Neither carriers of the minor allele of PTPN22 rs2476601 nor STAT4 rs7574 polymorphisms showed a significant association with a younger age at disease onset (P = 0.355, P = 0.065, respectively). We found an additive effect of the three genetic markers in the age at onset: subjects with three markers were associated with a disease onset 9.56, 8.61, and 6.41 years before than those with none, one, or two genetic markers (P = 0.004, P = 0.006 and P = 0.043, respectively). We also described the additive effect of shared epitope, anti-CCP antibodies, educational level, PTPN22, and STAT4 polymorphisms in age at onset. Patients with two, three, four, or five variables were associated with a significant younger age of disease onset (4.72 [0.05-9.38] years (P = 0.048), 9.56 [4.72-14.40] years (P < 0.0001), 12.74 [6.84-18.64] years (P < 0.0001), and 20.87 [10.40-37.17] years (P < 0.0001)). Risk factors for the development of rheumatoid arthritis are also associated, with an additive effect, with a younger age at disease onset.
Rheumatology International 09/2011; 32(10):3097-102. · 1.88 Impact Factor
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F David Carmona,
Aurora Serrano-Lopera,
Elena López-Isac,
Carmen P Simeón,
Patricia Carreira,
Raquel Rios-Fernandez,
Gerard Espinosa,
María Teresa Camps,
Nuria Navarrete,
María F González-Escribano, [......],
Rosa García-Portales,
María Victoria Egurbide,
Vicente Fonollosa,
Paloma García de la Peña,
Ana Pros,
Mónica Rodríguez-Carballeira,
Federico Díaz-Gónzalez,
Luis Sáez-Comet,
Miguel A González-Gay,
Javier Martín
Clinical and experimental rheumatology 09/2011; 29(5):895-6. · 2.15 Impact Factor
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Lara Bossini-Castillo,
Carmen P Simeon,
Lorenzo Beretta,
Madelon C Vonk,
José Luis Callejas-Rubio,
Gerard Espinosa,
Patricia Carreira,
María T Camps, Luis Rodríguez-Rodríguez,
Mónica Rodríguez-Carballeira, [......],
Paul Shiels,
Jacob M van Laar,
Carmen Fonseca,
Christopher Denton,
Ariane Herrick,
Jane Worthington,
Bobby P Koeleman,
Blanca Rueda,
Timothy R D J Radstake,
Javier Martin
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ABSTRACT: The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.
A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.
The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].
Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
Rheumatology (Oxford, England) 08/2011; 50(11):1976-81. · 4.24 Impact Factor
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ABSTRACT: The aim of our study was to analyze the influence of the CCR5Δ32 polymorphism in the risk of cardiovascular (CV) events and subclinical atherosclerosis among patients with rheumatoid arthritis (RA).
A total of 645 patients fulfilling the American Rheumatism Association 1987 revised classification criteria for RA were studied. Patients were genotyped for the CCR5 rs333 polymorphism using predesigned TaqMan assays. Also, HLA DRB1 genotyping was performed using molecular-based methods. Carotid intima-media thickness, flow-mediated endothelium-dependent dilatation (FMD) and endothelium-independent vasodilatation, which were used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients with no clinical CV disease.
A lower frequency of carriers of the CCR5Δ32 allele among patients with CV events (3.4% versus 11.3%, P = 0.025, odds ratio 0.28, 95% confidence interval (95% CI) 0.06 to 0.89) was observed. However, after adjusting for gender, age at time of RA diagnosis, and the presence of shared epitope, rheumatoid factor and classic CV risk factors in the Cox regression analysis, this reduction of CV events in CCR5Δ32 allele carriers was slightly outside the range of significance (P = 0.097; hazard ratio 0.37 (95% CI 0.12 to 1.19)). Carriers of the CCR5Δ32 deletion also showed higher FMD values than the remaining patients (CCR5/CCR5Δ32 patients: 7.03% ± 6.61% versus CCR5/CCR5 patients: 5.51% ± 4.66%). This difference was statistically significant when analysis of covariance was performed (P = 0.024).
Our results show a potential influence of the CCR5Δ32 deletion on the risk of CV disease among patients with RA. This may be due to a protective effect of this allelic variant against the development of vascular endothelial dysfunction.
Arthritis research & therapy 08/2011; 13(4):R133. · 4.27 Impact Factor
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F David Carmona,
Carmen P Simeon,
Lorenzo Beretta,
Patricia Carreira,
Madelon C Vonk,
Raquel Ríos-Fernández,
Gerard Espinosa,
Nuria Navarrete,
Esther Vicente-Rabaneda, Luis Rodríguez-Rodríguez, [......],
Raffaella Scorza,
Claudio Lunardi,
Jacob M van Laar,
Nicolas Hunzelmann,
Alexander Kreuter,
Ariane Herrick,
Jane Worthington,
Bobby P C Koeleman,
Timothy R D J Radstake,
Javier Martín
Annals of the rheumatic diseases 05/2011; 70(11):2050-2. · 8.11 Impact Factor
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ABSTRACT: To assess the potential association between LEP rs2167270 (19 G>A) gene polymorphism and disease susceptibility and cardiovascular disease (CV) in patients with rheumatoid arthritis (RA).
773 patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, and 957 matched controls, were studied. Patients were genotyped for the LEP rs2167270 (19G>A) polymorphism, located within the 5´UTR, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=133) and by B-mode ultrasonography of the carotid artery intima-media thickness (n=113).
No statistically significant differences in the genotype or allele frequencies of the LEP rs2167270 gene polymorphism between patients with RA and controls were seen. Likewise, LEP rs2167270 polymorphism did not influence the development of CV events. Also, no significant differences in LEP rs2167270 genotype or allele distribution were seen when results of surrogate markers of subclinical atherosclerosis were assessed.
LEP rs2167270 polymorphism does not seem to be a genetic risk factor for disease susceptibility or clinically evident CV disease and subclinical atherosclerosis in patients with RA.
Clinical and experimental rheumatology 03/2011; 29(2):293-8. · 2.15 Impact Factor
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ABSTRACT: Soluble interleukin-6 receptor α subunit (sIL-6R) is primarily generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A > C) resulting in an aspartic acid to alanine substitution (D358A) at the proteolytic cleavage site. The aim of this study was to determine whether plasma levels of sIL6R are influenced by the rs8192284 polymorphism in patients with rheumatoid arthritis and to assess the association between plasma sIL-6R levels and disease activity as reflected by anti-CCP status. Thirty-nine patients were randomly selected from a cohort of patients with RA of Spanish descent. Plasma sIL-6R concentrations were measured using sandwich ELISA. Genotyping of the rs8192284 (A > C) polymorphism was done using a Fast Real-Time PCR System. DAS 28 scores were used to assess disease activity. Plasma sIL-6R levels were positively associated with the number of C alleles (AA: 35.27 (3.50) ng/ml, AC: 45.50 (4.58) ng/ml, CC: 52.55 (3.18) ng/ml, P = 0.0001). DAS28 and plasma sIL-6R levels were positively associated in the anti-CCP-positive subgroup (r (2) = 0.45, P = 0.0336) and negatively associated in the anti-CCP-negative subgroup (r (2) = -0.45, P = 0.0825). No association between anti-CCP status and sIL-6R level was found. Our findings show that the rs8192284 polymorphism is operative in patients with RA. The presence of anti-CCP antibodies determines the relationship between sIL-6R concentration and disease activity.
Rheumatology International 03/2011; 31(3):409-13. · 1.88 Impact Factor
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ABSTRACT: To assess the influence of the TNFA rs1800629 (G > A) polymorphism in the risk of cardiovascular (CV) disease and subclinical atherosclerosis in patients with rheumatoid arthritis (RA).
587 patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were studied. Patients were genotyped for the TNFA rs1800629 polymorphism using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Carotid artery intima-media thickness, flow-mediated endothelium-dependent and endothelium independent vasodilatation, used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients.
We observed a higher frequency of carriers of the minor allele A among the patients with CV disease (with 37.6% vs. without 27.9%, p = 0.06, OR 1.56 [95% confidence interval-CI 0.95-2.54]). Carriers of the minor allele A exhibited a higher risk of CV events after adjustment for demographic and traditional CV risk factors (p = 0.023, HR 1.72 [95% CI 1.076-2.74]). Also, a significant interaction between this polymorphism and the presence of the rheumatoid shared epitope (SE) was observed (p = 0.024). Due to this, the association between carriers of the minor allele A and CV disease was only present in carriers of the SE, even after adjustment (p = 0.001, HR 2.43 [95% CI 1.41-4.19]). No significant association between the TNFA variant and the surrogate markers of subclinical atherosclerosis was observed.
Our results show that TNFA rs1800629 gene polymorphism is associated with predisposition to CV complications in patients with RA. This predisposition is restricted to individuals carrying the rheumatoid SE.
Atherosclerosis 02/2011; 216(1):125-30. · 3.79 Impact Factor
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Luis Rodríguez-Rodríguez,
Wan Rohani Wan Taib,
Ruth Topless,
Sophia Steer,
María F González-Escribano,
Alejandro Balsa,
Dora Pascual-Salcedo,
Miguel A González-Gay,
Enrique Raya,
Benjamín Fernandez-Gutierrez, [......],
Marte K Viken,
Marieke J H Coenen,
Piet L C M van Riel,
Barbara Franke,
Martin den Heijer,
Timothy R D J Radstake,
Paul Wordsworth,
Benedicte A Lie,
Tony R Merriman,
Javier Martín
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ABSTRACT: Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA).
RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5'-allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined.
The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel-Haenszel pooled OR 0.80 [95% CI 0.67-0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05-1.55], for 3 versus 1 risk allele P = 6.67 × 10(-11) , OR 2.01 [1.63-2.48], and for 4 versus 1 risk allele P = 6.50 × 10(-11) , OR 3.55 [2.42-5.20]).
Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well-established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.
Arthritis & Rheumatism 02/2011; 63(2):365-72. · 7.87 Impact Factor
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Luis Rodríguez-Rodríguez,
Francisco D Carmona,
Santos Castañeda,
José A Miranda-Filloy,
Inmaculada C Morado,
Javier Narváez,
Beatriz Marí-Alfonso,
Carmen Gómez-Vaquero,
Encarnación Amigo-Díaz,
Raquel Ríos-Fernández,
Ricardo Blanco,
Javier Llorca,
Benjamín Fernández-Gutiérrez,
Javier Martín,
Miguel A González-Gay
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ABSTRACT: To assess the potential association between the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms and giant cell arteritis (GCA). We also studied whether these polymorphisms might influence the phenotypic expression of GCA.
In total, 357 Spanish patients with biopsy-proven GCA and 574 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification.
Regarding the rs1343151 IL23R polymorphism, no significant differences in the genotype or allele frequencies between GCA patients and healthy controls were observed. The frequency of the minor allele A of the rs3790567 IL12RB2 variant was increased in GCA patients compared with controls (30.1% vs 25.7%, respectively; p = 0.039, OR 1.25, 95% CI 1.01-1.54). An increased frequency of subjects carrying the minor allele A (GA+AA genotypes) of the rs3790567 IL12RB2 polymorphism was found among GCA patients compared with controls (52.8% vs 44.4%; p = 0.013, OR 1.40, 95% CI 1.06-1.85). Although a higher frequency of the combination of minor alleles (A-A) in the subgroup of patients with visual ischemic complications compared with the combination of both major alleles (G-G; p = 0.029) or with the other allelic combinations (p = 0.035) was found, logistic regression analysis showed that this association was no longer significant after adjustment for potential confounding factors (A-A vs G-G: OR 2.10, 95% CI 0.88-5.04, p = 0.096).
Our results support a potential influence of the rs3790567 IL12RB2 polymorphism in the pathogenesis of GCA.
The Journal of Rheumatology 02/2011; 38(5):889-92. · 3.69 Impact Factor
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Clinical and experimental rheumatology 01/2011; 29(1):142-3. · 2.15 Impact Factor
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Luis Rodríguez-Rodríguez,
Santos Castañeda,
Tomás R Vázquez-Rodríguez,
Inmaculada C Morado,
Carmen Gómez-Vaquero,
Beatriz Marí-Alfonso,
José Alberto Miranda-Filloy,
Javier Narvaez,
Norberto Ortego-Centeno,
Esther F Vicente,
Ricardo Blanco,
Encarnación Amigo-Diaz,
Benjamín Fernández-Gutiérrez,
Javier Martin,
Miguel A González-Gay
[show abstract]
[hide abstract]
ABSTRACT: To assess the influence of the interleukin (IL)2-IL21 rs6822844 G/T polymorphism in the susceptibility to biopsy-proven giant cell arteritis (GCA) and in the clinical spectrum of manifestations of this vasculitis.
Two hundred and seventy-two biopsy-proven GCA patients were included in this study. DNA from patients and matched controls (n=791) was obtained from peripheral blood. Samples were genotyped for the rs6822844 polymorphism using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification.
No significant differences in the allele and genotype frequencies between biopsy-proven GCA patients and controls were observed. However, the stratification of GCA patients disclosed some differences according to gender and ischemic manifestations of the disease. In this regard, the frequency of the minor allele T was increased in males (14.8%) compared to females (8.4%) (odds ratio-OR:1.89 (95% confidence interval-CI: 1.09-3.28); p=0.02; Bonferroni adjustment p=0.12). Also, minor allele T frequency was increased in GCA patients with severe ischemic complications (12.8%) compared to those without severe ischemic complications (7.7%) (OR:1.72 (95% CI: 0.97-3.05); p=0.05; Bonferroni adjustment p=0.30), and specifically in patients with jaw claudication (13.7% versus 8.2% in those without jaw claudication; OR:1.76 (95% CI: 1.02-3.04); p=0.04; Bonferroni adjustment p=0.24).
IL2-IL21 rs6822844 polymorphism does not appear to be a genetic risk factor for susceptibility to biopsy-proven GCA. However, this gene polymorphism may contribute to the different phenotypic expression of this vasculitis, in particular in the development of ischemic complications of the disease.
Clinical and experimental rheumatology 12/2010; 29(1 Suppl 64):S12-6. · 2.15 Impact Factor
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Luis Rodríguez-Rodríguez,
Santos Castañeda,
Tomás R Vázquez-Rodríguez,
Inmaculada C Morado,
Beatriz Marí-Alfonso,
Carmen Gómez-Vaquero,
José A Miranda-Filloy,
Norberto Ortego-Centeno,
Javier Narvaez,
Ricardo Blanco,
Benjamín Fernández-Gutiérrez,
Javier Martín,
Miguel A González-Gay
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[hide abstract]
ABSTRACT: To assess the influence of the IL2RA rs2104286 A>G polymorphism on susceptibility to and clinical spectrum of manifestations of biopsy-proven giant cell arteritis (GCA).
Our study included 318 patients with biopsy-proven GCA. DNA from patients and healthy controls was obtained from peripheral blood. Samples were genotyped for the IL2RA rs2104286 A>G polymorphism using a predesigned TaqMan allele discrimination assay and by PCR amplification.
Although GCA patients showed a higher frequency of the minor allele homozygote of IL2RA rs2104286 (GG) compared to controls (5.1% vs 2.8%, respectively; p = 0.06, odds ratio 1.84, 95% confidence interval 0.91-3.70), the allele distribution showed no significant differences between GCA patients and controls. Stratification of GCA patients according to sex or polymyalgia rheumatica, jaw claudication, visual ischemic manifestations, or other severe ischemic complications did not yield significant differences in the allele or genotype frequencies of the IL2RA rs2104286 polymorphism.
IL2RA rs2104286 polymorphism does not appear to be a genetic risk factor for susceptibility to biopsy-proven GCA. Also, this polymorphism does not seem to be implicated in the clinical expression of this vasculitis.
The Journal of Rheumatology 11/2010; 37(11):2331-3. · 3.69 Impact Factor
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Luis Rodríguez-Rodríguez,
Santos Castañeda,
Tomás R Vázquez-Rodríguez,
Inmaculada C Morado,
Beatriz Marí-Alfonso,
Carmen Gómez-Vaquero,
José A Miranda-Filloy,
Javier Narvaez,
Norberto Ortego-Centeno,
Ricardo Blanco,
Benjamín Fernández-Gutiérrez,
Javier Martín,
Miguel A González-Gay
[show abstract]
[hide abstract]
ABSTRACT: To assess the potential association between CD40 rs1883832 polymorphism and biopsy-proven giant cell arteritis (GCA). We also studied the influence of the polymorphism on phenotypic expression of this vasculitis, in particular the development of visual ischemic manifestations.
Three hundred five Spanish patients with biopsy-proven GCA and 788 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the CD40 rs1883832 C/T polymorphism using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification.
Patients with GCA showed a trend toward a higher frequency of the minor allele homozygote of rs1883832 (TT) compared to healthy controls (12.1% vs 8.3%, respectively; p = 0.05, OR 1.54, 95% CI 0.98-2.40). Also, a marginally significant increased frequency of the minor allele T was observed in patients with GCA who had visual ischemic manifestations (36.9%) compared to those without visual ischemic manifestations (27.7%; p = 0.04, OR 1.53, 95% CI 0.99-2.34). In this regard, patients with GCA carrying the minor allele T (either TT or TC) experienced visual ischemic manifestations more commonly than those carrying the CC genotype (58.5% vs 44.2%; p = 0.04, OR 1.78, 95% CI 0.99-3.22).
Our results suggest a potential implication of the CD40 rs1883832 C/T polymorphism in susceptibility to visual ischemic manifestations in individuals with biopsy-proven GCA.
The Journal of Rheumatology 10/2010; 37(10):2076-80. · 3.69 Impact Factor
