RESUMO
Objectives: The aim of our study was to investigate whether TNFAIP3, PTPN22, and TRAF1-5 single nucleotide polymorphisms (SNPs) are associated with susceptibility, severity, or serological markers in primary Sjögren's syndrome (pSS). Patients and methods: The cases and controls study was conducted between December 2021 and June 2022. TNFAIP3 rs10499194C/T, rs6920220G/A, and rs2230926T/G, PTPN22 rs2476601C/T and rs33996649G/A, and TRAF1-C5 rs10818488G/A polymorphisms were genotyped in 154 female pSS patients (mean age: 45.2±6.8 years) and 313 female control subjects (mean age: 50.3±7.5 years) using the TaqMan® SNP genotyping assay. An association analysis between TNFAIP3, PTPN22, and TRAF1-C5 SNPs and susceptibility, clinical characteristics, and serological markers of pSS was performed. Interactions between TNFAIP3, PTPN22, and TRAF1-C5 SNPs were also evaluated in patients and controls. Results: The genotype and allele frequencies showed no association with susceptibility, severity, or serological markers of pSS. Nevertheless, several interactions between TNFAIP3 and TRAF1-C5 or TNFAIP3, PTPN22, and TRAF1-C5 genotypes were associated with susceptibility to pSS (p<0.01). Conclusion: Individual TNFAIP3, PTPN22, and TRAF1-C5 SNPs are not associated with susceptibility, severity, or serological markers of pSS. However, genetic interactions between TRAF1-C5 and TNFAIP3 or TNFAIP3, PTPN22, and TRAF1-C5 SNPs are risk factors for pSS.
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No disponible.
Assuntos
COVID-19 , Pró-Calcitonina , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Ferritinas , Humanos , Unidades de Terapia Intensiva , Precursores de Proteínas , SARS-CoV-2RESUMO
The AIRE gene influences the expression of a wide array of self-antigens in the thymus, and is essential to the negative selection of self-reactive T cells and establishment of central tolerance. Single nucleotide variants (SNVs) such as rs878081C/T (Ser196Ser) and rs2075876G/T at this locus have been associated with susceptibility to rheumatoid arthritis, mainly in Asian populations, but its role in systemic lupus erythematosus (SLE) has not been documented. We performed a case-control association study with 379 SLE patients and 460 controls from central Mexico. In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico. In the first group, we identified that the AIRE Ser196Ser synonymous variant was associated with SLE (OR 1.4, pâ¯=â¯0.009), meanwhile, in the second group we observed the following: OR 1.7, pâ¯=â¯0.024. No association was found between these AIRE SNVs and lupus nephritis. Our results suggest that AIRE is a risk factor for SLE in our population. This study is the first to document an association between AIRE and SLE susceptibility.
Assuntos
Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Fatores de Transcrição/genética , Artrite Reumatoide/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/genética , México , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Linfócitos T/imunologia , Proteína AIRERESUMO
Los microRNA (miRNA) son pequeños RNA no codificantes de aproximadamente 17 a 24 nucleótidos de longitud, los cuales se unen complementaria y principalmente en las regiones 3' UTR (región no traducida) de diversos RNA mensajeros (mRNA, messenger RNA). Su función general es regular negativamente la expresión génica a nivel postranscripcional, inhibiendo la traducción. Perfiles de expresión de miRNA alterados han sido identificados en diferentes líquidos, células y tejidos humanos afectados con diversas enfermedades autoinmunes y algunos se han propuestos potencialmente como biomarcadores de diagnóstico, pronóstico, actividad, etcétera, en estas patologías. Adicionalmente, variantes comunes del genoma humano, denominados polimorfismos de un solo nucleótido (SNP, single nucleotide polymorphisms) localizados en genes de miRNA han sido asociados con susceptibilidad, gravedad, y actividad en estas enfermedades. El objetivo de esta revisión es describir la biogénesis de los miRNA, su función, así como los perfiles de expresión y SNP en genes de miRNA asociados con diversas enfermedades autoinmunes, incluyendo tiroiditis autoinmune (tiroiditis de Hashimoto y enfermedad de Graves), lupus eritematoso sistémico, artritis reumatoide y síndrome de Sjögren primario.
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 17-24 nucleotides in length, which complementarily and mainly bind in 3' UTR (untranslated region) regions of different messenger RNAs (mRNAs). Their general function is to negatively regulate gene expression at the posttranscriptional level, thus inhibiting translation. miRNA abnormal expression profiles of have been found in different human fluids, cells and tissues affected by different autoimmune diseases, and some of them have been proposed as potential biomarkers of diagnosis, prognosis, activity etc. in these pathologies. In addition, common variants of the human genome, called single-nucleotide polymorphisms (SNPs), located within miRNA genes, have been associated with susceptibility, severity and activity in these diseases. The purpose of this review is to describe miRNA biogenesis and function, as well as the expression profiles and SNPs in miRNA genes that are associated with different autoimmune diseases, including autoimmune thyroiditis (HashimotoMs thyroiditis and Gravess disease), systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.
Assuntos
Doenças Autoimunes/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Humanos , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de DoençaRESUMO
Resumen Los microRNA (miRNA) son pequeños RNA no codificantes de aproximadamente 17 a 24 nucleótidos de longitud, los cuales se unen complementaria y principalmente en las regiones 3' UTR (región no traducida) de diversos RNA mensajeros (mRNA, messenger RNA). Su función general es regular negativamente la expresión génica a nivel postranscripcional, inhibiendo la traducción. Perfiles de expresión de miRNA alterados han sido identificados en diferentes líquidos, células y tejidos humanos afectados con diversas enfermedades autoinmunes y algunos se han propuestos potencialmente como biomarcadores de diagnóstico, pronóstico, actividad, etcétera, en estas patologías. Adicionalmente, variantes comunes del genoma humano, denominados polimorfismos de un solo nucleótido (SNP, single nucleotide polymorphisms) localizados en genes de miRNA han sido asociados con susceptibilidad, gravedad, y actividad en estas enfermedades. El objetivo de esta revisión es describir la biogénesis de los miRNA, su función, así como los perfiles de expresión y SNP en genes de miRNA asociados con diversas enfermedades autoinmunes, incluyendo tiroiditis autoinmune (tiroiditis de Hashimoto y enfermedad de Graves), lupus eritematoso sistémico, artritis reumatoide y síndrome de Sjögren primario.
Abstract MicroRNAs (miRNAs) are small non-coding RNAs of approximately 17-24 nucleotides in length, which complementarily and mainly bind in 3' UTR (untranslated region) regions of different messenger RNAs (mRNAs). Their general function is to negatively regulate gene expression at the posttranscriptional level, thus inhibiting translation. miRNA abnormal expression profiles of have been found in different human fluids, cells and tissues affected by different autoimmune diseases, and some of them have been proposed as potential biomarkers of diagnosis, prognosis, activity etc. in these pathologies. In addition, common variants of the human genome, called single-nucleotide polymorphisms (SNPs), located within miRNA genes, have been associated with susceptibility, severity and activity in these diseases. The purpose of this review is to describe miRNA biogenesis and function, as well as the expression profiles and SNPs in miRNA genes that are associated with different autoimmune diseases, including autoimmune thyroiditis (HashimotoMs thyroiditis and Gravess disease), systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.
Assuntos
Humanos , Doenças Autoimunes/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/imunologia , Índice de Gravidade de Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. METHODS: The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. RESULTS: The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio = 0.6, pc = 0.0051) but not with SLE (odds ratio = 0.7, pc = 0.13). CONCLUSIONS: The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.
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Artrite Reumatoide/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos de Casos e Controles , Simulação por Computador , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , México , Pessoa de Meia-Idade , Razão de Chances , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The TNF -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms have consistently been associated with systemic lupus erythematosus (SLE) in several populations; however, these findings have not been verified in all populations. Here, we aimed to examine whether the TNF -238G/A, -308G/A, -376G/A (rs1800750), and -1031T/C (rs1799964) polymorphisms confer SLE or lupus nephritis (LN) susceptibility in a Mexican population. Our study included 442 patients with SLE and 495 controls. For genotyping, we used the TaqMan 5' allele discrimination assay. The TNF -238G/A and -1031T/C polymorphisms were associated with SLE susceptibility (odds ratio (OR) 2.1, p = 0.0005 and OR 1.4, p = 0.003, respectively). Gender stratification showed a strong association between TNF -238G/A and SLE in women (OR 2.2, p = 0.00006), while TNF -1031T/C had an OR of 1.5 (p = 0.007). With regard to the TNF -376G/A polymorphism, this also showed association with SLE susceptibility (OR 1.95, p = 0.036) and LN (OR 3.5, p = 0.01). In conclusion, our study provides the first demonstration of association between the TNF -376G/A polymorphism and SLE and LN susceptibility. In addition, our study is the second documenting an association of TNF -1031T/C with SLE susceptibility. We also observed a strong association between TNF -238G/A and SLE susceptibility. The TNF 308G/A polymorphism was not associated with SLE or LN.
Assuntos
Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Nefrite Lúpica/genética , Masculino , México , Pessoa de Meia-IdadeRESUMO
Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Different genetic variants including the TNF -308G/A polymorphism are associated with RA susceptibility. However, these findings have not been replicated in all populations. The aim of this study was to determine whether the TNF -1031T/C (rs1799964), -376G/A (rs1800750), -308G/A (rs1800629) -238G/A (rs361525), and TNFR1 -609G/T polymorphisms are associated with RA susceptibility in a sample of Mexican patients. Our study included 499 patients with RA and 492 healthy controls. The genotypes of the TNF polymorphisms were obtained using TaqMan assay. The genotype and allele frequencies of the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms were similar among RA cases versus healthy controls, and no association with RA susceptibility was identified. Our results suggest that the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms are not associated with RA susceptibility in a sample of Mexican patients.