RESUMO
OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858CâT) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.
Assuntos
Doenças Inflamatórias Intestinais/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Estudos de Coortes , Colite Ulcerativa/genética , Doença de Crohn/genética , Humanos , Marrocos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. METHODS: The distribution of (TAAA)n_rs12720460 and (CCTTT)n _rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan® allelic discrimination technology. RESULTS: The allele and genotype frequencies of HIF1A_ rs11549467, NFKB1_rs28362491 and NOS2A_ (TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A_ (CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P = 0.02; OR = 1.71, 95%CI: 1.07-2.74), (CCTTT)14 (P = 0.02; OR = 1.71, 95%CI: 1.06-2.76) alleles in IBD, (CCTTT)8 (P = 0.008; OR = 1.95, 95%CI: 1.17-3.23) in CD and (CCTTT)7 (P = 0.009; OR = 7.61, 95%CI: 1.25-46.08), (CCTTT)11 (P = 0.05; OR = 0.51, 95%CI: 0.25-1.01), (CCTTT)14 (P = 0.02; OR = 2.05, 95%CI: 1.07-3.94), (CCTTT)15 (P = 0.01; OR = 2.25, 95%CI: 1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size. CONCLUSION: Our results suggest that the NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.
Assuntos
Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Doenças Inflamatórias Intestinais/genética , Subunidade p50 de NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/genética , Adolescente , Adulto , Alelos , Feminino , Haplótipos , Humanos , Masculino , Repetições de Microssatélites/genética , Marrocos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto JovemAssuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/genética , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Proteínas NLRRESUMO
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Our data do not support a role of the rs540386 TRAF6 variant as a key component of the genetic network underlying SSc and GCA.
Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Polimorfismo de Nucleotídeo Único , Esclerodermia Difusa/genética , Esclerodermia Limitada/genética , Fator 6 Associado a Receptor de TNF/genética , Doenças Autoimunes/diagnóstico , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/imunologia , Humanos , Masculino , Fatores de Risco , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/imunologiaRESUMO
OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Autoimunidade/genética , Arterite de Células Gigantes/genética , Polimorfismo de Nucleotídeo Único , Idoso , Biópsia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Testes Genéticos , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/patologia , Haplótipos , Humanos , Masculino , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Medição de Risco , Fatores de Risco , Espanha/epidemiologiaRESUMO
OBJECTIVE: To investigate whether a functional integrin alpha M (ITGAM) variant is involved in susceptibility to and clinical manifestations of giant cell arteritis (GCA). METHODS: A Spanish cohort of 437 white patients with biopsy-proven GCA and 1388 healthy controls were genotyped using the TaqMan allele discrimination technology. RESULTS: 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. CONCLUSION: Our results suggest that the ITGAM rs1143679 variant does not play an important role in the pathophysiology of GCA.
