Progress in Gasdermin B gene and its related diseases / 中华微生物学和免疫学杂志

Human Gasdermin B (GSDMB) gene, as a member of the Gasdermin (GSDM) gene family, may be associated with the development of asthma, tumor and immune system diseases. Recent studies have found that cell pyroptosis can be mediated by GSDMB protein. The N-terminus of GSDMB cleaved by Granzyme A (GZMA), which is secreted by cytotoxic lymphocytes, can directly promote cell pyroptosis. Moreover, GSDMB protein promotes the cleavage of Gasdermin D (GSDMD) by binding to cysteinyl aspartate specific proteinase-4 (caspase-4), thus indirectly promoting cell pyroptosis. This article summarized the progress in the mechanism of GSDMB gene-mediated cell pyroptosis and the related diseases.

The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis

PURPOSE: ORM1-like 3 (ORMDL3) belongs to a highly conserved protein family which is anchored as transmembrane protein in the endoplasmic reticulum. Gasdermin B (GSDMB) is adjacent to ORMDL3 on chromosome 17q21.2 and belongs to the gasdermin-domain containing the protein family (GSDM family). Recent reports suggest that GSDMB and ORMDL3 are associated with asthma in several populations. However, genetic association studies that examined the association of GSDMB and ORMDL3 gene variants with asthma showed conflicting results. To assess whether combined evidence shows the association between GSDMB/ORMDL3 polymorphism and asthma. METHODS: A bibliographic search from MEDLINE identified 13 original articles using the search keywords 'GSDMB', 'ORMDL3', and 'asthma'. An updated literature-based meta-analysis involving 6,691 subjects with asthma, 9,281 control individuals, and 1,360 families were conducted. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on the fixed effects model or the random effects model depended on Cochran's Q-statistic and I2 values. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. RESULTS: We selected and identified 3 SNPs of ORMDL3 associated with asthma (rs8076131: OR=1.10; 95% CI, 1.02-1.20; P=0.012. rs12603332: OR=1.15; 95% CI, 1.05-1.25; P=0.002. rs3744246: OR=1.10; 95% CI, 1.02-1.17; P=0.008) and 1 SNP of GSDMB associated with asthma (rs7216389: OR=1.37; 95% CI, 1.27-1.47; P<0.01). Publication bias was estimated using modified Egger's linear regression test proposed by Harbordetal and revealed no evidence of biases. Furthermore, cumulative meta-analysis in chronological order showed the inclination toward significant association for rs7216389 and rs12603332 with continually adding studies, and the inclination toward null-significant association for rs3744246 and rs8076131. CONCLUSIONS: Moderate evidence exists for associations of the ORMDL3 rs8076131, rs12603332, and rs3744246 and GSDMB rs7216389 variants with asthma. Large sample size and representative population-based studies and TDT studies with homogeneous asthmatic patients and well-matched controls are warranted to confirm this finding.

ORMDL3/GSDMB polymorphism and childhood asthma susceptibility:a Meta-analysis / 中华实用儿科临床杂志

Objective To investigate the relationship between ORMDL3/GSDMB polymorphism and genetic susceptibility to childhood asthma.Methods The electronic databases PubMed,Wanfang,China National Knowledge Infrastructure (CNKI),Weipu,and China Biology Medicinedisc (CBM) were browsed for published case-control studies on investigating the association between ORMDL3/GSDMB polymorphism and genetic susceptibility to childhood asthma.Odds ratio(OR) and 95％ confidence interval (95％ CI) were used to investigate the strength of the association.Fixed or random effect models were selected for pooled OR calculation.Publication bias was assessed.All statistical analysis was conducted with Review Manager 5.0 software.Results Six case-control studies with a total of 3289 childhood asthma cases and 3391 controls were included.For the homozygote TT and T allele carriers (TT + TC),the pooled ORs (95％ CI) were 1.86 (1.58-2.20) and 1.56 (1.35-1.80) compared to the homozygous genotype (CC).In the stratified analysis by ethnicity,the ORs (95％ CI) of the T allele carriers and the homozygote TT were 1.50(1.15-1.96) and 1.51 (1.15-1.98) among Asians.While among European,the ORs (95％ CI) of the T allele carriers and the homozygote TT were 1.69 (1.42-2.02) and 2.11 (1.71-2.61).Conclusions ORMDL3/GSDMB polymorphism is overall associated with childhood asthma susceptibility.However,the susceptibility in the Asians is a little lower compared with that of the European populations,which suggest a possible role of ethnic differences in genetic backgrounds.