Association of the rs17250932, rs4794067, and rs2240017 polymorphism in the TBX21 gene with autoimmune diseases: A meta-analysis

Objective: To evaluate systematically the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations. Methods: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger’s regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis. Results: A total of 12 eligible studies, including 3834 patients and 4824 healthy controls, were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms were significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131–1.875, P = 0.004; OR: 0.766, 95% CI: 0.615–0.954, P = 0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239–2.189, P = 0.001; OR: 0.796, 95% CI: 0.634–0.999, P = 0.049), and dominant model (OR: 1.572, 95% CI: 1.194–2.071, P = 0.004; OR: 0.767, 95% CI: 0.607–0.970, P = 0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases, and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was established in this meta-analysis. Conclusion: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphism confer susceptibility to autoimmune diseases, but not rs17250932 (AU)

Effect of ginger extract on expression of GATA3, T-bet and ROR-yt in peripheral blood mononuclear cells of patients with Allergic Asthma

Introduction and objectives: Allergic asthma is a chronic inflammatory disorder of the airways. Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma. The function of these cells is affected by T-bet, GATA3 and RORgammat transcription factors (respectively). Therefore, the aim of this study was to evaluate the effect of ginger (officinal Roscoe) extract on the expression of T-bet, GATA-3 and ROR-gamma in peripheral blood mononuclear cells (PBMC) of asthmatic patients, in comparison with healthy volunteers as controls. Materials and methods: In this case-control study, a total of 50 individuals including 25 patients with severe, moderate and mild allergic asthma and 25 unrelated healthy controls were involved. The PBMCs were isolated and divided into four groups: negative control, two positive controls (Budesonide and PHA) and ginger-extract treated group. After cell treatment and incubation for 48h, PBMCs were isolated and cDNA was synthesized. Gene expressions of T-bet, GATA3 and ROR-γt were evaluated by Real-time PCR. Results: According to the results of this study, hydroalcoholic extract of ginger could reduce the expression of GATA-3, ROR-gammat, and T-bet in PBMCs of asthmatic patients in comparison with untreated PBMCs (P values = 0.001, 0.001, and 0.002, respectively). It was also shown that the ginger extract could affect T-bet/GATA-3, T-bet/ROR-gamma, and ROR-gammat/GATA-3 expression ratios. Conclusions: This study showed that the use of ginger extract could control asthma and decrease the severity of this disease by affecting the main cells involving the symptoms of asthma in the airways

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Síndrome de Holt-Oram: caracterización de una nueva mutación / Holt-Oram syndrome: characterization of a novel mutation

Introducción Los síndromes cardiomiélicos comprenden cardiopatías congénitas y malformaciones esqueléticas de los miembros superiores, y están relacionados con mutaciones deletéreas de factores de transcripción con dominios del tipo T-Box. El síndrome de Holt-Oram se debe a una mutación dominante en el gen TBX5 que altera la estructura tridimensional de la proteína impidiendo su correcta unión al ADN. Se han descrito varias mutaciones puntuales y deleciones de TBX5 en pacientes con fenotipo de síndrome de Holt-Oram. Pacientes y métodos El paciente es un niño con una comunicación interauricular (CIA) del tipo ostium secundum grande y una comunicación interventricular (CIV) diagnosticados por clínica (soplo) y ecocardiografía. Presenta además unos dedos pulgares algo hipoplásicos y con un emplazamiento distal bilateral, con un índice de implantación de 0,19 frente a una media normal de 0,50 para su edad gestacional al nacer. Es remitido a la consulta de Genética para descartar microdeleción 22q11.2. Resultados El cariotipo y la hibridación in situ de fluorescencia (FISH) con sonda D22S75 resultaron normales y debido a los hallazgos clínicos se realizó un estudio molecular para el síndrome de Holt-Oram. Se encontró una mutación en el intrón 7 de TBX5 que produce una probable alteración del splicing del gen que da lugar a una proteína truncada en su extremo C-terminal. Los padres del propósito presentan una secuencia normal para el gen, lo que indica que la mutación se produjo de novo, sin que pueda descartarse un mosaicismo germinal en los padres. Conclusiones El síndrome de Holt-Oram es la causa más frecuente de síndrome cardiomiélico. Debería ser objeto de estudio molecular todo niño con malformaciones cardíacas y alteraciones de las extremidades superiores como pulgares ausentes, hipoplásicos, distalmente emplazados o trifalángicos

Introduction Cardiomyelic syndromes encompass congenital heart disease and skeletal malformations of the upper limbs and are related to mutations in transcription factors with T-Box domains. Holt-Oram syndrome is caused by a dominant mutation in the TBX5 gene that alters the three-dimensional structure of the protein and its DNA binding function. Several point mutations and deletions in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype. Patients and methods The proband was a boy with a large atrial septal defect ostium secundum type and a ventricular septal defect, diagnosed by clinical findings (heart murmur) and echocardiography. He also presented slightly hypoplastic thumbs with distal bilateral placement and an implantation index of 0.19 (compared with an average of 0.50 for his gestational age at birth). The boy was referred to the department of medical genetics to rule out 22q11.2 microdeletion syndrome. Results Karyotype and fluorescence in situ hybridization at locus D22S75 were both normal. Because of his clinical findings, molecular study for Holt-Oram syndrome was indicated, leading to the finding of a mutation at intron 7 of TBX5, probably producing a splicing alteration of the gene and resulting in a protein truncated at its C-terminal end. The proband's parents presented the wild type sequence of the gene, thus indicating that the mutation was produced de novo, although a possible germinal mosaicism in the parents could not be ruled out. Conclusions Holt-Oram syndrome is the most frequent cause of cardiomyelic syndrome. All children with heart malformations and abnormalities of the upper limbs such as absent, hypoplastic, distally placed or triphalangic thumbs should undergo molecular studies for this syndrome