Other entities represented in this entry:
HGNC Approved Gene Symbol: ASRT8
Cytogenetic location: 9q33 Genomic coordinates (GRCh38) : 9:114,900,001-127,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 9q33 | {Asthma-related traits, susceptibility to, 8} | 613207 | 2 |
For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807.
Matsuda et al. (2005) found an association between adult asthma and a SNP within the fibronectin type III-D (Fn-III-D) domain of the TNC gene in a case-control study of 446 Japanese adult asthmatic patients and 658 healthy Japanese controls. The 44513A-T SNP in exon 17 strongly associated with adult bronchial asthma (P = 0.00019, odds ratio = 1.76) and results in a leu1677-to-ile (L1677I) substitution within the Fn-III-D domain of the alternative splicing region. As the TNC fibronectin-III domain has molecular elasticity, the authors suggested that the structural change may affect the integrity and stiffness of asthmatic airways.
Orsmark-Pietras et al. (2008) identified tenascin C as a downstream target gene of NPS (609513)-NPSR1 (608595) signaling in transfected HEK-293H cells and in a human lung epithelial cell line. Both the TNC and NPSR1 proteins showed increased expression in the bronchial epithelium of patients with asthma compared to controls. Variation in the NPSR1 gene on chromosome 7p15-p14 has previously been associated with susceptibility to asthma (ASRT2; 608584). By genotyping SNPs from the midpart of the TNC gene to the 3-prime region in 3,113 Western European children with asthma-related disorders, Orsmark-Pietras et al. (2008) found significant associations between several SNPs and haplotypes in the TNC gene. The most significant association was between rhinoconjunctivitis and rs3789873 in intron 10 (OR, 1.41; p = 0.002). When restricted to allergic rhinoconjunctivitis, defined as a combination of current rhinoconjunctivitis and the presence of IgE antibodies to inhalant allergens, the association with rs3789873 was still significant (OR, 1.37; p = 0.008). Weaker associations were seen with other phenotypes, including a doctor's diagnosis of asthma and atopic sensitization. Haplotype analysis yielded a stronger association with rhinoconjunctivitis (OR, 1.49; p = 0.0005), as well as lesser but still significant associations with allergic rhinoconjunctivitis, allergic asthma, and atopic sensitization. No significant associations were found on either single SNP or haplotype analysis for wheezing or atopic eczema. Further analysis showed evidence of an epistatic interaction between TNC and NPSR1 variants. The TNC variant rs2104772 (L1677I), in combination with NPSR1 SNPs rs323922 and rs324384, showed significant interactions for atopic sensitization or doctor's diagnosis for asthma (p values ranging from 0.009 to 0.037). Orsmark-Pietras et al. (2008) postulated that tenascin C might be an important factor in incomplete healing and remodeling of asthmatic airways. The findings suggested that TNC is a candidate gene for childhood rhinoconjunctivitis, an asthma-related trait, and that there may be an epistatic interaction between 2 functionally related genes.
Matsuda, A., Hirota, T., Akahoshi, M., Shimizu, M., Tamari, M., Miyatake, A., Takahashi, A., Nakashima, K., Takahashi, N., Obara, K., Yuyama, N., Doi, S., and 11 others. Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma. Hum. Molec. Genet. 14: 2779-2786, 2005. [PubMed: 16115819] [Full Text: https://doi.org/10.1093/hmg/ddi311]
Orsmark-Pietras, C., Melen, E., Vendelin, J., Bruce, S., Laitinen, A., Laitinen, L. A., Lauener, R., Riedler, J., von Mutius, E., Doekes, G., Wickman, M., van Hage, M., Pershagen, G., Scheynius, A., Nyberg, F., Kere, J., PARSIFAL Genetics Study Group. Biological and genetic interaction between tenascin C and neuropeptide S receptor 1 in allergic diseases. Hum. Molec. Genet. 17: 1673-1682, 2008. [PubMed: 18305139] [Full Text: https://doi.org/10.1093/hmg/ddn058]