rs7216389
badMag 6.5This is a intron variant variant in the GSDMB gene.
Key Literature Trait Associations
Childhood Asthma
rs7216389 is located in intron 1 of GSDMB within the 17q21 locus, the most replicated genetic risk locus for childhood-onset asthma. The T allele is associated with increased expression of ORMDL3 and GSDMB, genes involved in sphingolipid metabolism and epithelial cell pyroptosis, respectively. This variant was identified in the landmark GWAS by Moffatt et al. (2007) and has been consistently replicated across European and multi-ethnic cohorts.
Asthma
Beyond childhood-specific analyses, rs7216389 T allele confers increased asthma risk in adult populations as well. A 13-study meta-analysis (6,462 cases, 7,357 controls) found significant association in the overall population. Another large meta-analysis of GSDMB/ORMDL3 variants (13 studies, 6,691 asthmatic subjects, 9,281 controls, 1,360 families) yielded OR = 1.37 (95% CI 1.27–1.47). Effect sizes are consistent across multiple genetic models and ethnic subgroups, making this one of the most replicated asthma GWAS loci.
Chronic rhinosinusitis
rs7216389 T allele is associated with increased susceptibility to chronic rhinosinusitis (CRS), extending the inflammatory airway phenotype beyond lower respiratory disease. A multi-institutional cohort study and meta-analysis across two academic centers (399 CRS cases, 341 controls) found OR = 1.40 (95% CI 1.16–1.76, P = 0.004). This is biologically plausible given that GSDMB/ORMDL3 expression drives airway epithelial inflammation affecting both upper and lower airways.
Atopic multimorbidity
rs7216389 T allele increases the likelihood of co-occurring atopic conditions (eczema, wheeze, and rhinitis together) across childhood and early adulthood. A four-birth-cohort study (2,079 children followed to early adulthood) found 1.4- to 1.7-fold increased odds of multimorbid atopic disease in T carriers, even when individual conditions were not independently associated. This suggests the 17q21 locus promotes a systemic atopic trajectory rather than disease-specific effects alone.
Allergic rhinitis
Variants at the 17q21 locus including rs7216389 have been associated with allergic rhinitis, particularly in Japanese and East Asian populations. A study in the Japanese population found that ORMDL3 transcript levels were significantly correlated with rs7216389 genotype (P < 0.01), and five 17q21 polymorphisms jointly associated with allergic rhinitis (combined P = 0.00074). Evidence is somewhat population-specific and less consistent than for asthma; one COPSAC birth cohort study found no independent rhinitis association once asthma was accounted for.
▶GWAS Catalog Trait Associations (1)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (1)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
asthma
▶Research that mentions this SNP (3)
▶Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetesAssociationN=10,320Nada M. Saleh et al.(2011)· Diabetes/Metabolism Research and Reviews
This candidate gene association study examined genetic variants in atopic disease and proinflammatory cytokine genes for association with type 1 diabetes in 6,743-10,320 cases and 7,864-9,354 controls. The FLG R501X/rs61816761 (p=0.82), SELS -105/rs28665122 (p=0.08), and IL18 SNPs showed no association with T1D. However, four loci previously associated with asthma also showed significant association with T1D: HLA, GSDMB/ORMDL3/GSDMA (rs2305480, rs3894194, p≤1.2×10⁻⁶), and IL2RB (rs2284033, p=0.005), suggesting shared genetic susceptibility between atopic and autoimmune diseases.
▶Allergy and glioma risk: Test of association by genotypeAssociationN=5,548Sara E. Dobbins et al.(2011)· International Journal of Cancer
Case-control genome-wide association study of 1,878 glioma cases and 3,670 controls examining associations between asthma/allergy susceptibility variants and glioma risk. SNP rs7216389 at 17q21 (ORMDL3) was significantly associated with increased glioma risk (OR=1.10, 95% CI: 1.01-1.19, P=0.022), providing genetic evidence for a positive association between asthma susceptibility and glioma risk, contrary to epidemiological studies reporting inverse associations.
▶Polymorphisms in GSDMA and GSDMB are associated with asthma susceptibility, atopy and BHRAssociationN=1,300Jinho Yu et al.(2011)· Pediatric Pulmonology
This case-control study of 1,300 Korean children examined associations between GSDMA rs7212938 (Leu128Val) and GSDMB rs7216389 polymorphisms with childhood asthma susceptibility and intermediate phenotypes (elevated IgE and bronchial hyperresponsiveness). The risk allele combinations showed significant associations with asthma (aOR 1.36-1.68), atopic asthma, and elevated IgE/BHR levels, suggesting additive effects from GSDMA and GSDMB variants in asthma pathogenesis.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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