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Objective@#To investigate the association of ORMDL3 gene polymorphism with the risk of bronchial asthma of Uygur people in Urumqi region. @*Methods@#Ten single nucleotide polymorphism (SNP) loci of ORMDL3 gene in 93 Uygur patients with bronchial asthma and 100 healthy controls were genotyped by the multiplex SNP (SNaPshot) technique, and the association of different genotypes and alleles with the risk of asthma of Uygur people was analyzed. @*Results@#There were significant differences in genotype and allele frequencies of rs7216389 and rs12603332 loci of ORMDL3 gene between asthma patients and healthy controls (P＜0.05). The detection data of SNP loci of ORMDL3 gene were all in accordance with Hardy-Weiberg law (P＞0.05). @*Conclusion@#The polymorphism of ORMDL3 gene is directly associated with the risk of asthma in Uygur people, and the rs7216389 and rs12603332 loci of ORMDL3 gene may be the susceptible sites of bronchial asthma in Uygur people.
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Objective To discuss the polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing,in order to provide a theoretical basis for early diagnosis of asthma.Methods One hundred and fifty wheezing infants were recruited and divided into 2 groups as asthma predictive index(API) positive group(n =80) and negative group (n =70).Taqman probe was applied to detect the genotypes of 2 single nucleotide polymorphisms (SNPs)in childhood asthma susceptibility gene ORMDL3,which were rs4794820 and rs7216389.The genotype distributions were analyzed and compared between 2 groups,and the correlations among genotype distribution and tidal breath pulmonary function,fractional exhaled nitric oxide (FeNO) concentration,percentage of eosinophils (EOS％),serum immune globulin E (total IgE) levels respectively were also analyzed,respectively.Results (1) The frequencies of rs4794820 AG and rs7216389 TC heterozygotes in the API positive group were the highest,which were significantly higher than those in the negative group(58.75％ vs.31.42％,56.25％ vs.32.86％ respectively,all P ＜0.01).The frequencies of GG and TT homozygotes in the API negative group were the highest,which were significantly higher than those in the positive group (58.57％ vs.30.00％,57.14％ vs.31.25％ respectively,all P ＜0.01).(2)The time to reach the peak expiratory flow in tidal breathing over the total expiratory time (TPTEF/TE) and the volume to reach the peak expiratory flow in tidal breathing over the total expiratory volume (VPEF/VE) of the infants in the API positive group were less than those in the API negative group(16.87 ±5.31 vs.20.12 ± 5.23,20.87 ± 5.92 vs.25.56 ± 6.77,respectively),and the FeNO concentration was higher than that in the API negative group [(22.44 ± 9.77) ppb vs.(13.23 ± 7.90)ppb],and the differences were significant (t =-3.776,-4.490,6.377,respectively;all P ＜ 0.01).(3) In the API positive group,the TPTEF/TE and VPEF/VE of the infants who expressed AG/TC genotype were lower than those who expressed GG/TT genotype (14.55 ± 4.83 vs.19.91 ± 4.17,18.85 ± 4.26 vs.25.20 ± 7.06,respectively,t =-4.727,-3.976,all P ＜ 0.01);while the FeNO concentrations,EOS％ and total IgE levels were higher than those who expressed GG/TT genotype [(25.02 ± 8.77) ppb vs.(18.39 ± 6.56) ppb,7.16 ± 2.62 vs.5.50 ± 1.34,(366 727 ±275 533) IU/L vs.(166 826 ± 62 865) IU/L,respectively] (t =3.484,3.409,4.589 respectively;all P ＜ 0.01).Conclusions Childhood asthma susceptibility gene ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors for API positive infantile wheezing.The pulmonary function damage and airway inflammation of the infants who expressed AG/TC genotype are more serious than those who expressed GG/TT genotype,and more likely to develop persistent asthma.
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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.
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Humans , Asthma , Bias , Case-Control Studies , Endoplasmic Reticulum , Genetic Association Studies , Linear Models , Polymorphism, Single Nucleotide , Publication Bias , Sample SizeABSTRACT
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.
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@#ObjectiveTo explore the relationship between ORMDL3 gene polymorphism and Asthma in children.Methods178 cases of children with asthma were divided into mild group and severe group, and 129 cases of children were treated as normal control group who tested blood samples in the PLA General Hospital and its Affiliated Hospital in the recent 4 years. ORMDL3 gene locus rs7216389 genotype was detected, including PCR, restriction endonuclease analysis and bio-statistical aspects of analysis.ResultsThere was significant difference (P<0-05) in 3 genotypes (CC＼TC＼TT). There was no significant difference in TT between the mild group and the control group (P>0-05). The rate of severe group was higher than that in the mild and the control groups(P<0-05). Asthmas in children showed higher T allele frequency.ConclusionORMDL3 gene polymorphism showed a certain relevance with asthma in children.