biostudies-literatureUnknown9Shrestha Palikhe NWestern UniversityCanadian Allergy, Asthma and Immunology FoundationCanadian Institutes of Health Research<h4>Background</h4>CRTh2 is G protein coupled receptor for prostaglandin D2 (PGD)₂ expressed by immune cells that drive type 2 inflammation such as CD4⁺ T cells (Th2), eosinophils and group 2 innate lymphoid cells (ILC2) as well as structural cells including smooth muscle and epithelium. CRTh2-expressing cells are increased in the blood and airways of asthmatics and severe asthma is characterized by increased activity of the PGD₂-CRTh2 pathway. The <i>CRTh2</i> single nucleotide polymorphism (SNP) rs533116 G > A is associated with development of asthma and increased Th2 cell differentiation.<h4>Objective</h4>To examine whether CRTh2 rs533116G > A associates with asthma severity. Since severe asthma is more common in females than males, we performed a sex-stratified analysis.<h4>Methods</h4>Clinical data from asthmatics (<i>n</i> = 170) were obtained from clinic visits and chart review. Asthma severity was assessed according to ERS/ATS guidelines. Peripheral blood cells were characterized by flow cytometry and qRT-PCR. Genotyping was performed by TaqMan assay.<h4>Results</h4>Older females (≥45 years) homozygous for minor A allele of rs533116 were more likely to have severe asthma, lower FEV₁, a higher prescribed dose of inhaled corticosteroid and more type 2 inflammation than females carrying GA or GG genotypes. Comparing females and males with the AA genotype also revealed that women had more type 2 inflammation.<h4>Conclusions and significance</h4>The polymorphism CRTh2 rs533116 G > A associates with severe asthma and type 2 inflammation in older females. This study reveals a gene-sex-aging interaction influencing the effect of CRTh2 on asthma severity.Frontiers in medicine970495https://www.ebi.ac.uk/biostudies/studies/S-EPMC9606418biostudies-literatureThe CRTh2 polymorphism rs533116 G > A associates with asthma severity in older females.PMC9606418Cameron LVliagoftis HKim RBShrestha Palikhe NMackenzie CALicskai CfalseThe CRTh2 polymorphism rs533116 G > A associates with asthma severity in older females.<h4>Background</h4>CRTh2 is G protein coupled receptor for prostaglandin D2 (PGD)₂ expressed by immune cells that drive type 2 inflammation such as CD4⁺ T cells (Th2), eosinophils and group 2 innate lymphoid cells (ILC2) as well as structural cells including smooth muscle and epithelium. CRTh2-expressing cells are increased in the blood and airways of asthmatics and severe asthma is characterized by increased activity of the PGD₂-CRTh2 pathway. The <i>CRTh2</i> single nucleotide polymorphism (SNP) rs533116 G > A is associated with development of asthma and increased Th2 cell differentiation.<h4>Objective</h4>To examine whether CRTh2 rs533116G > A associates with asthma severity. Since severe asthma is more common in females than males, we performed a sex-stratified analysis.<h4>Methods</h4>Clinical data from asthmatics (<i>n</i> = 170) were obtained from clinic visits and chart review. Asthma severity was assessed according to ERS/ATS guidelines. Peripheral blood cells were characterized by flow cytometry and qRT-PCR. Genotyping was performed by TaqMan assay.<h4>Results</h4>Older females (≥45 years) homozygous for minor A allele of rs533116 were more likely to have severe asthma, lower FEV₁, a higher prescribed dose of inhaled corticosteroid and more type 2 inflammation than females carrying GA or GG genotypes. Comparing females and males with the AA genotype also revealed that women had more type 2 inflammation.<h4>Conclusions and significance</h4>The polymorphism CRTh2 rs533116 G > A associates with severe asthma and type 2 inflammation in older females. This study reveals a gene-sex-aging interaction influencing the effect of CRTh2 on asthma severity.2022-01-01T00:00:00Z20222026-05-03T10:32:48.639Z2025-05-29T16:10:59.711ZS-EPMC96064183631402810.3389/fmed.2022.970495