Genetic effects of multiple asthma loci identified by genomewide association studies on asthma and spirometric indices

Tang

Pediatric Allergy Immunology

et al. 2017

Section: Discussionsupporting

confidence: 90%

“…Many studies reported genes on 17q21 locus, such as ORMDL3 and GSDMB , to be the most widely replicated asthma genes in different ethnic groups . The recent GWAS also reported GSDMB to be associated with severe asthma exacerbations in Swedish preschool children .…”

Section: Discussionmentioning

confidence: 99%

Trajectory of spirometric and exhaled nitric oxide measurements in Chinese schoolchildren with asthma

Tang

Pediatric Allergy Immunology

et al. 2017

Pediatric Allergy Immunology

“…It is now clear that the manifestations of allergic disorders are the results of complex interactions between genetic and environmental factors. Using both the candidate gene and the genomewide association approaches, many studies of genetics susceptibilities for allergic disorders in Chinese have been performed . As exemplified by studies of asthma genetic studies, there are substantial differences in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes in Chinese and other populations .…”

Section: International Collaboration and Research In Chinamentioning

confidence: 99%

“…Using both the candidate gene and the genomewide association approaches, many studies of genetics susceptibilities for allergic disorders in Chinese have been performed. [28][29][30][31][32] As exemplified by studies of asthma genetic studies, there are substantial differences in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes in Chinese and other populations. 33 As demonstrated by the complexity of the interaction between polymorphisms of the CD14 gene and exposures to microbes on the risk of asthma, 34 future international collaborative efforts with simultaneous assessment of relevant environmental exposures are needed to clearly understand the contribution of various susceptibility genes in the pathogenesis of allergic disorders in different ethnic groups.…”

Section: International Collaboration and Research In Chinamentioning

confidence: 99%

Pediatric allergy and immunology in China

Wong

Bao

et al. 2017

Self Cite

Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide.

Proc. Natl. Acad. Sci. U.S.A.

“…The overexpression of GSDMC in metastatic melanoma cells is an exception to its apoptotic role (9). In addition to cancer, genome-wide association studies (GWAS) have revealed a correlation between single nucleotide polymorphisms (SNPs) in both the protein coding and transcriptional regulatory regions of the neighboring genes GSDMA, GSDMB, and ORDML3 in the 17q12.2.1 loci and susceptibility to diseases such as asthma (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), type 1 diabetes (21,22), Crohn's disease, ulcerative colitis (22,23), and rheumatoid arteritis (22,24). The mechanisms by which these SNPs affect susceptibility to developing complex-trait inflammatory diseases are unknown.…”

mentioning

confidence: 99%

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein

Chao

Kulakova

Herzberg

2017

150

189

The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N-and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88 DNVD 91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.GSDMB | X-ray crystallography | disease risk polymorphism | complex trait inflammatory disease | lipid binding