Allergy Asthma Immunol Res.  2015 Mar;7(2):175-185. 10.4168/aair.2015.7.2.175.

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

• Zhao CN
• Fan Y
• Huang JJ
• Zhang HX
• Gao T
• Wang C
• Wang T
• Hou LF

• KMID: 2365546
• DOI: http://doi.org/10.4168/aair.2015.7.2.175

Abstract

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.

Keyword

GSDMB; ORMDL3; polymorphism; asthma; meta-analysis

MeSH Terms

Asthma*
Bias (Epidemiology)
Case-Control Studies
Endoplasmic Reticulum
Genetic Association Studies
Humans
Linear Models
Polymorphism, Single Nucleotide
Publication Bias
Sample Size

Figure

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  Fig. 1 Results of meta-analysis of associations between ORMDL3 variants and asthma risk. (A) Forest plot for rs3744246 using the random-effects model. (B) Forest plot for rs8076131 using the fixed effects model.

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  Fig. 2 Results of meta-analysis of associations between GSDMB and ORMDL3 variants and asthma risk. (A) Forest plot for rs7216389 using the random-effects model. (B) Forest plot for rs12603332 using the fixed effects model.

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  Fig. 3 Results of cumulative meta-analysis of associations between ORMDL3 variants and asthma risk. (A) Cumulative forest plot for rs3744246 using the random-effects model. (B) Cumulative forest plot for rs8076131 using the fixed effects model.

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  Fig. 4 Results of cumulative meta-analysis of associations between GSDMB and ORMDL3 variants and asthma risk. (A) Cumulative forest plot for rs7216389 using the random-effects model. (B) Cumulative forest plot for rs12603332 using the fixed effects model.

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